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Cancer RNome: Evolution and Sustenance

  • Mansi Arora
  • Deepak Kaul
Chapter

Abstract

Neoplastic transformation is the result of accumulation of numerous genetic and epigenetic alterations that convert a normal cell into a cancer cell and confers it with an ability to proliferate and sustain indefinitely. The increasing acknowledgement of the non-coding RNAs (ncRNAs) as important players (as opposed to transcriptional noise) in the gene regulation has prompted the researchers across the globe to shift their focus from the “protein-coding genes” to ncRNAs. Several studies have explicitly demonstrated that ncRNAs are differentially expressed in cancer cells and their dysregulation is associated with malignant transformation. In this chapter, we discuss the various established and emerging hallmarks of cancer in light of ncRNAs that are intertwined with pathways of tumor progression. An increased understanding of this transcriptional complexity of cancer cells will definitely open up fresh avenues for cancer diagnosis and treatment.

Keywords

Cancer hallmarks Cancer immunology Deregulated energetics Genomic instability ncRNA deregulation Replicative immortality 

References

  1. Abbas T, Keaton MA, Dutta A (2013) Genomic instability in cancer. Cold Spring Harb Perspect Biol 5:a012914.  https://doi.org/10.1101/cshperspect.a012914CrossRefPubMedPubMedCentralGoogle Scholar
  2. Aguilera A, García-Muse T (2012) R loops: from transcription byproducts to threats to genome stability. Mol Cell 46:115–124.  https://doi.org/10.1016/j.molcel.2012.04.009CrossRefPubMedPubMedCentralGoogle Scholar
  3. Akincilar SC, Unal B, Tergaonkar V (2016) Reactivation of telomerase in cancer. Cell Mol Life Sci 73:1659–1670.  https://doi.org/10.1007/s00018-016-2146-9CrossRefPubMedPubMedCentralGoogle Scholar
  4. Amin ARMR, Karpowicz PA, Carey TE et al (2015) Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds. Semin Cancer Biol 35(Suppl):S55–S77.  https://doi.org/10.1016/j.semcancer.2015.02.005CrossRefPubMedPubMedCentralGoogle Scholar
  5. Ancrile B, Lim K-H, Counter CM (2007) Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev 21:1714–1719.  https://doi.org/10.1101/gad.1549407CrossRefPubMedPubMedCentralGoogle Scholar
  6. Andersson S, Wallin K-L, Hellström A-C et al (2006) Frequent gain of the human telomerase gene TERC at 3q26 in cervical adenocarcinomas. Br J Cancer 95:331–338.  https://doi.org/10.1038/sj.bjc.6603253CrossRefPubMedPubMedCentralGoogle Scholar
  7. Andrae J, Gallini R, Betsholtz C (2008) Role of platelet-derived growth factors in physiology and medicine. Genes Dev 22:1276–1312.  https://doi.org/10.1101/gad.1653708CrossRefPubMedPubMedCentralGoogle Scholar
  8. Anwar SL, Krech T, Hasemeier B et al (2015) Loss of DNA methylation at imprinted loci is a frequent event in hepatocellular carcinoma and identifies patients with shortened survival. Clin Epigenetics 7:110.  https://doi.org/10.1186/s13148-015-0145-6CrossRefPubMedPubMedCentralGoogle Scholar
  9. Anwar SL, Wulaningsih W, Lehmann U (2017) Transposable elements in human cancer: causes and consequences of deregulation. Int J Mol Sci.  https://doi.org/10.3390/ijms18050974PubMedCentralCrossRefGoogle Scholar
  10. Arima T, Kamikihara T, Hayashida T et al (2005) ZAC, LIT1 (KCNQ1OT1) and p57KIP2 (CDKN1C) are in an imprinted gene network that may play a role in Beckwith-Wiedemann syndrome. Nucleic Acids Res 33:2650–2660.  https://doi.org/10.1093/nar/gki555CrossRefPubMedPubMedCentralGoogle Scholar
  11. Armanios M, Greider CW (2005) Telomerase and cancer stem cells. Cold Spring Harb Symp Quant Biol 70:205–208.  https://doi.org/10.1101/sqb.2005.70.030CrossRefPubMedPubMedCentralGoogle Scholar
  12. Arnoult N, Van Beneden A, Decottignies A (2012) Telomere length regulates TERRA levels through increased trimethylation of telomeric H3K9 and HP1α. Nat Struct Mol Biol 19:948–956.  https://doi.org/10.1038/nsmb.2364CrossRefPubMedPubMedCentralGoogle Scholar
  13. Arora M, Kaul D, Sharma YP (2014a) Human coronary heart disease: importance of blood cellular miR-2909 RNomics. Mol Cell Biochem 392:49–63.  https://doi.org/10.1007/s11010-014-2017-3CrossRefPubMedPubMedCentralGoogle Scholar
  14. Arora R, Lee Y, Wischnewski H et al (2014b) RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells. Nat Commun 5:5220.  https://doi.org/10.1038/ncomms6220CrossRefPubMedPubMedCentralGoogle Scholar
  15. Artandi SE, DePinho RA (2010) Telomeres and telomerase in cancer. Carcinogenesis 31:9–18.  https://doi.org/10.1093/carcin/bgp268CrossRefPubMedPubMedCentralGoogle Scholar
  16. Ashkenazi A, Dixit VM (1999) Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 11:255–260PubMedCrossRefPubMedCentralGoogle Scholar
  17. Avilion AA, Piatyszek MA, Gupta J et al (1996) Human telomerase RNA and telomerase activity in immortal cell lines and tumor tissues. Cancer Res 56:645–650PubMedPubMedCentralGoogle Scholar
  18. Azoulay-Zohar H, Israelson A, Abu-Hamad S, Shoshan-Barmatz V (2004) In self-defence: hexokinase promotes voltage-dependent anion channel closure and prevents mitochondria-mediated apoptotic cell death. Biochem J 377:347–355.  https://doi.org/10.1042/BJ20031465CrossRefPubMedPubMedCentralGoogle Scholar
  19. Azzalin CM, Lingner J (2015) Telomere functions grounding on TERRA firma. Trends Cell Biol 25:29–36.  https://doi.org/10.1016/j.tcb.2014.08.007CrossRefPubMedPubMedCentralGoogle Scholar
  20. Azzalin CM, Reichenbach P, Khoriauli L et al (2007) Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 318:798–801.  https://doi.org/10.1126/science.1147182CrossRefPubMedPubMedCentralGoogle Scholar
  21. Bae NS, Baumann P (2007) A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends. Mol Cell 26:323–334.  https://doi.org/10.1016/j.molcel.2007.03.023CrossRefPubMedPubMedCentralGoogle Scholar
  22. Baeriswyl V, Christofori G (2009) The angiogenic switch in carcinogenesis. Semin Cancer Biol 19:329–337.  https://doi.org/10.1016/j.semcancer.2009.05.003CrossRefPubMedPubMedCentralGoogle Scholar
  23. Baffy G (2010) Uncoupling protein-2 and cancer. Mitochondrion 10:243–252.  https://doi.org/10.1016/j.mito.2009.12.143CrossRefPubMedPubMedCentralGoogle Scholar
  24. Bai C, Connolly B, Metzker ML et al (2000) Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster. Proc Natl Acad Sci U S A 97:1230–1235PubMedPubMedCentralCrossRefGoogle Scholar
  25. Balk B, Maicher A, Dees M et al (2013) Telomeric RNA-DNA hybrids affect telomere-length dynamics and senescence. Nat Struct Mol Biol 20:1199–1205.  https://doi.org/10.1038/nsmb.2662CrossRefPubMedPubMedCentralGoogle Scholar
  26. Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252.  https://doi.org/10.1038/32588CrossRefPubMedPubMedCentralGoogle Scholar
  27. Barthel A, Okino ST, Liao J et al (1999) Regulation of GLUT1 gene transcription by the serine/threonine kinase Akt1. J Biol Chem 274:20281–20286PubMedCrossRefPubMedCentralGoogle Scholar
  28. Bartocci C, Diedrich JK, Ouzounov I et al (2014) Isolation of chromatin from dysfunctional telomeres reveals an important role for Ring1b in NHEJ-mediated chromosome fusions. Cell Rep 7:1320–1332.  https://doi.org/10.1016/j.celrep.2014.04.002CrossRefPubMedPubMedCentralGoogle Scholar
  29. Baumann M, Kappl A, Lang T et al (1990) The diagnostic validity of the serum tumor marker phosphohexose isomerase (PHI) in patients with gastrointestinal, kidney, and breast cancer. Cancer Investig 8:351–356CrossRefGoogle Scholar
  30. Baur JA, Zou Y, Shay JW, Wright WE (2001) Telomere position effect in human cells. Science 292:2075–2077.  https://doi.org/10.1126/science.1062329CrossRefPubMedPubMedCentralGoogle Scholar
  31. Beasley RP, Hwang LY, Lin CC, Chien CS (1981) Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet (Lond) 2:1129–1133CrossRefGoogle Scholar
  32. Beckerman R, Prives C (2010) Transcriptional regulation by p53. Cold Spring Harb Perspect Biol 2:a000935.  https://doi.org/10.1101/cshperspect.a000935CrossRefPubMedPubMedCentralGoogle Scholar
  33. Beckers A, Organe S, Timmermans L et al (2007) Chemical inhibition of acetyl-CoA carboxylase induces growth arrest and cytotoxicity selectively in cancer cells. Cancer Res 67:8180–8187.  https://doi.org/10.1158/0008-5472.CAN-07-0389CrossRefPubMedPubMedCentralGoogle Scholar
  34. Bell RJA, Rube HT, Xavier-Magalhães A et al (2016) Understanding TERT Promoter Mutations: a Common Path to Immortality. Mol Cancer Res 14:315–323.  https://doi.org/10.1158/1541-7786.MCR-16-0003CrossRefPubMedPubMedCentralGoogle Scholar
  35. Beloribi-Djefaflia S, Vasseur S, Guillaumond F (2016) Lipid metabolic reprogramming in cancer cells. Oncogene 5:e189.  https://doi.org/10.1038/oncsis.2015.49CrossRefGoogle Scholar
  36. Beltrán-Anaya FO, Cedro-Tanda A, Hidalgo-Miranda A, Romero-Cordoba SL (2016) Insights into the regulatory role of non-coding RNAs in cancer metabolism. Front Physiol 7:342.  https://doi.org/10.3389/fphys.2016.00342CrossRefPubMedPubMedCentralGoogle Scholar
  37. Benetti R, García-Cao M, Blasco MA (2007) Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres. Nat Genet 39:243–250.  https://doi.org/10.1038/ng1952CrossRefPubMedPubMedCentralGoogle Scholar
  38. Bennett MW, O’Connell J, O’Sullivan GC et al (1998) The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma. J Immunol 160:5669–5675PubMedPubMedCentralGoogle Scholar
  39. Bermudez Y, Erasso D, Johnson NC et al (2006) Telomerase confers resistance to caspase-mediated apoptosis. Clin Interv Aging 1:155–167PubMedPubMedCentralCrossRefGoogle Scholar
  40. Bermudez Y, Yang H, Saunders BO et al (2007) VEGF- and LPA-induced telomerase in human ovarian cancer cells is Sp1-dependent. Gynecol Oncol 106:526–537.  https://doi.org/10.1016/j.ygyno.2007.05.005CrossRefPubMedPubMedCentralGoogle Scholar
  41. Berteaux N, Lottin S, Monté D et al (2005) H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1. J Biol Chem 280:29625–29636.  https://doi.org/10.1074/jbc.M504033200CrossRefPubMedPubMedCentralGoogle Scholar
  42. Bertozzi D, Iurlaro R, Sordet O et al (2011) Characterization of novel antisense HIF-1α transcripts in human cancers. Cell Cycle Georget Tex 10:3189–3197.  https://doi.org/10.4161/cc.10.18.17183CrossRefGoogle Scholar
  43. Bhaumik D, Patil CK, Campisi J (2009) MicroRNAs: an important player in maintaining a balance between inflammation and tumor suppression. Cell Cycle Georget Tex 8:1822Google Scholar
  44. Bhutia YD, Babu E, Ramachandran S, Ganapathy V (2015) Amino Acid transporters in cancer and their relevance to “glutamine addiction”: novel targets for the design of a new class of anticancer drugs. Cancer Res 75:1782–1788.  https://doi.org/10.1158/0008-5472.CAN-14-3745CrossRefPubMedPubMedCentralGoogle Scholar
  45. Bielenberg DR, Zetter BR (2015) The contribution of angiogenesis to the process of metastasis. Cancer J Sudbury Mass 21:267–273.  https://doi.org/10.1097/PPO.0000000000000138CrossRefGoogle Scholar
  46. Biffi G, Tannahill D, Balasubramanian S (2012) An intramolecular G-quadruplex structure is required for binding of telomeric repeat-containing RNA to the telomeric protein TRF2. J Am Chem Soc 134:11974–11976.  https://doi.org/10.1021/ja305734xCrossRefPubMedPubMedCentralGoogle Scholar
  47. Blesson S, Thiery J, Gaudin C et al (2002) Analysis of the mechanisms of human cytotoxic T lymphocyte response inhibition by NO. Int Immunol 14:1169–1178PubMedCrossRefPubMedCentralGoogle Scholar
  48. Bollrath J, Greten FR (2009) IKK/NF-kappaB and STAT3 pathways: central signalling hubs in inflammation-mediated tumour promotion and metastasis. EMBO Rep 10:1314–1319.  https://doi.org/10.1038/embor.2009.243CrossRefPubMedPubMedCentralGoogle Scholar
  49. Bommer GT, Gerin I, Feng Y et al (2007) p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol 17:1298–1307.  https://doi.org/10.1016/j.cub.2007.06.068CrossRefPubMedPubMedCentralGoogle Scholar
  50. Borchert GM, Holton NW, Larson ED (2011) Repression of human activation induced cytidine deaminase by miR-93 and miR-155. BMC Cancer 11:347.  https://doi.org/10.1186/1471-2407-11-347CrossRefPubMedPubMedCentralGoogle Scholar
  51. Borrego F, Kabat J, Kim D-K et al (2002) Structure and function of major histocompatibility complex (MHC) class I specific receptors expressed on human natural killer (NK) cells. Mol Immunol 38:637–660PubMedCrossRefPubMedCentralGoogle Scholar
  52. Boshart M, Gissmann L, Ikenberg H et al (1984) A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. EMBO J 3:1151–1157PubMedPubMedCentralCrossRefGoogle Scholar
  53. Bosma MJ, Carroll AM (1991) The SCID mouse mutant: definition, characterization, and potential uses. Annu Rev Immunol 9:323–350.  https://doi.org/10.1146/annurev.iy.09.040191.001543CrossRefPubMedPubMedCentralGoogle Scholar
  54. Bottai G, Pasculli B, Calin GA, Santarpia L (2014) Targeting the microRNA-regulating DNA damage/repair pathways in cancer. Expert Opin Biol Ther 14:1667–1683.  https://doi.org/10.1517/14712598.2014.950650CrossRefPubMedPubMedCentralGoogle Scholar
  55. Boyington JC, Sun PD (2002) A structural perspective on MHC class I recognition by killer cell immunoglobulin-like receptors. Mol Immunol 38:1007–1021PubMedCrossRefPubMedCentralGoogle Scholar
  56. Bozza PT, Viola JPB (2010) Lipid droplets in inflammation and cancer. Prostaglandins Leukot Essent Fatty Acids 82:243–250.  https://doi.org/10.1016/j.plefa.2010.02.005CrossRefPubMedPubMedCentralGoogle Scholar
  57. Brait M, Sidransky D (2011) Cancer epigenetics: above and beyond. Toxicol Mech Methods 21:275–288.  https://doi.org/10.3109/15376516.2011.562671CrossRefPubMedPubMedCentralGoogle Scholar
  58. Bronte V, Serafini P, Mazzoni A et al (2003) L-arginine metabolism in myeloid cells controls T-lymphocyte functions. Trends Immunol 24:302–306PubMedCrossRefPubMedCentralGoogle Scholar
  59. Bruno T, De Angelis R, De Nicola F et al (2002) Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb. Cancer Cell 2:387–399PubMedCrossRefPubMedCentralGoogle Scholar
  60. Bueno MJ, Malumbres M (2011) MicroRNAs and the cell cycle. Biochim Biophys Acta 1812:592–601.  https://doi.org/10.1016/j.bbadis.2011.02.002CrossRefPubMedPubMedCentralGoogle Scholar
  61. Bueno MJ, Pérez de Castro I, Malumbres M (2008) Control of cell proliferation pathways by microRNAs. Cell Cycle Georget Tex 7:3143–3148.  https://doi.org/10.4161/cc.7.20.6833CrossRefGoogle Scholar
  62. Bulut-Karslioglu A, De La Rosa-Velázquez IA, Ramirez F et al (2014) Suv39h-dependent H3K9me3 marks intact retrotransposons and silences LINE elements in mouse embryonic stem cells. Mol Cell 55:277–290.  https://doi.org/10.1016/j.molcel.2014.05.029CrossRefPubMedPubMedCentralGoogle Scholar
  63. Burkholder B, Huang R-Y, Burgess R et al (2014) Tumor-induced perturbations of cytokines and immune cell networks. Biochim Biophys Acta 1845:182–201.  https://doi.org/10.1016/j.bbcan.2014.01.004CrossRefPubMedPubMedCentralGoogle Scholar
  64. Burnet FM (1970) The concept of immunological surveillance. Prog Exp Tumor Res 13:1–27PubMedCrossRefPubMedCentralGoogle Scholar
  65. Burnet FM (1971) Immunological surveillance in neoplasia. Transplant Rev 7:3–25PubMedPubMedCentralGoogle Scholar
  66. Butz H, Likó I, Czirják S et al (2010) Down-regulation of Wee1 kinase by a specific subset of microRNA in human sporadic pituitary adenomas. J Clin Endocrinol Metab 95:E181–E191.  https://doi.org/10.1210/jc.2010-0581CrossRefPubMedPubMedCentralGoogle Scholar
  67. Cairns RA, Harris IS, Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11:85–95.  https://doi.org/10.1038/nrc2981CrossRefPubMedPubMedCentralGoogle Scholar
  68. Calado RT, Cooper JN, Padilla-Nash HM et al (2012) Short telomeres result in chromosomal instability in hematopoietic cells and precede malignant evolution in human aplastic anemia. Leukemia 26:700–707.  https://doi.org/10.1038/leu.2011.272CrossRefPubMedPubMedCentralGoogle Scholar
  69. Calin GA, Dumitru CD, Shimizu M et al (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99:15524–15529.  https://doi.org/10.1073/pnas.242606799CrossRefPubMedPubMedCentralGoogle Scholar
  70. Calin GA, Sevignani C, Dumitru CD et al (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 101:2999–3004.  https://doi.org/10.1073/pnas.0307323101CrossRefPubMedPubMedCentralGoogle Scholar
  71. Cantor JR, Sabatini DM (2012) Cancer cell metabolism: one hallmark, many faces. Cancer Discov 2:881–898.  https://doi.org/10.1158/2159-8290.CD-12-0345CrossRefPubMedPubMedCentralGoogle Scholar
  72. Carnero A, Hannon GJ (1998) The INK4 family of CDK inhibitors. Curr Top Microbiol Immunol 227:43–55PubMedPubMedCentralGoogle Scholar
  73. Caro P, Kishan AU, Norberg E et al (2012) Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma. Cancer Cell 22:547–560.  https://doi.org/10.1016/j.ccr.2012.08.014CrossRefPubMedPubMedCentralGoogle Scholar
  74. Cascio S, D’Andrea A, Ferla R et al (2010) miR-20b modulates VEGF expression by targeting HIF-1 alpha and STAT3 in MCF-7 breast cancer cells. J Cell Physiol 224:242–249.  https://doi.org/10.1002/jcp.22126CrossRefPubMedPubMedCentralGoogle Scholar
  75. Catalina-Rodriguez O, Kolukula VK, Tomita Y, et al (2012) The mitochondrial citrate transporter, CIC, is essential for mitochondrial homeostasis. Oncotarget 3:1220–1235. doi: 10.18632/oncotarget.714Google Scholar
  76. Cavalli LR, Varella-Garcia M, Liang BC (1997) Diminished tumorigenic phenotype after depletion of mitochondrial DNA. Cell Growth Differ Mol Biol J Am Assoc Cancer Res 8:1189–1198Google Scholar
  77. Cederbaum SD, Yu H, Grody WW et al (2004) Arginases I and II: do their functions overlap? Mol Genet Metab 81(Suppl 1):S38–S44.  https://doi.org/10.1016/j.ymgme.2003.10.012CrossRefPubMedPubMedCentralGoogle Scholar
  78. Cerhan JR, Ansell SM, Fredericksen ZS et al (2007) Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma. Blood 110:4455–4463.  https://doi.org/10.1182/blood-2007-05-088682CrossRefPubMedPubMedCentralGoogle Scholar
  79. Chaabane W, User SD, El-Gazzah M et al (2013) Autophagy, apoptosis, mitoptosis and necrosis: interdependence between those pathways and effects on cancer. Arch Immunol Ther Exp (Warsz) 61:43–58.  https://doi.org/10.1007/s00005-012-0205-yCrossRefGoogle Scholar
  80. Chakrabarti M, Banik NL, Ray SK (2013) miR-138 overexpression is more powerful than hTERT knockdown to potentiate apigenin for apoptosis in neuroblastoma in vitro and in vivo. Exp Cell Res 319:1575–1585.  https://doi.org/10.1016/j.yexcr.2013.02.025CrossRefPubMedPubMedCentralGoogle Scholar
  81. Chang Y-C, Hsu T-L, Lin H-H et al (2004) Modulation of macrophage differentiation and activation by decoy receptor 3. J Leukoc Biol 75:486–494.  https://doi.org/10.1189/jlb.0903448CrossRefPubMedPubMedCentralGoogle Scholar
  82. Chang S, Wang R-H, Akagi K et al (2011) Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155. Nat Med 17:1275–1282.  https://doi.org/10.1038/nm.2459CrossRefPubMedPubMedCentralGoogle Scholar
  83. Chen S, Wang H, Ng WL et al (2011) Radiosensitizing effects of ectopic miR-101 on non-small-cell lung cancer cells depend on the endogenous miR-101 level. Int J Radiat Oncol Biol Phys 81:1524–1529.  https://doi.org/10.1016/j.ijrobp.2011.05.031CrossRefPubMedPubMedCentralGoogle Scholar
  84. Chen B, Li H, Zeng X et al (2012a) Roles of microRNA on cancer cell metabolism. J Transl Med 10:228.  https://doi.org/10.1186/1479-5876-10-228CrossRefPubMedPubMedCentralGoogle Scholar
  85. Chen H, Untiveros GM, McKee LAK et al (2012b) Micro-RNA-195 and -451 regulate the LKB1/AMPK signaling axis by targeting MO25. PLoS One.  https://doi.org/10.1371/journal.pone.0041574PubMedPubMedCentralCrossRefGoogle Scholar
  86. Chen L, Li Y, Lin CH et al (2013) Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma. Nat Med 19:209–216.  https://doi.org/10.1038/nm.3043CrossRefPubMedPubMedCentralGoogle Scholar
  87. Chen L, Gibbons DL, Goswami S et al (2014a) Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nat Commun 5:5241.  https://doi.org/10.1038/ncomms6241CrossRefPubMedPubMedCentralGoogle Scholar
  88. Chen L, Lü M-H, Zhang D et al (2014b) miR-1207-5p and miR-1266 suppress gastric cancer growth and invasion by targeting telomerase reverse transcriptase. Cell Death Dis 5:e1034.  https://doi.org/10.1038/cddis.2013.553CrossRefPubMedPubMedCentralGoogle Scholar
  89. Chen Y, Williams V, Filippova M et al (2014c) Viral carcinogenesis: factors inducing DNA damage and virus integration. Cancer 6:2155–2186.  https://doi.org/10.3390/cancers6042155CrossRefGoogle Scholar
  90. Chen Y, Li C, Tan C, Liu X (2016) Circular RNAs: a new frontier in the study of human diseases. J Med Genet 53:359–365.  https://doi.org/10.1136/jmedgenet-2016-103758CrossRefPubMedPubMedCentralGoogle Scholar
  91. Chiarugi P, Cirri P (2016) Metabolic exchanges within tumor microenvironment. Cancer Lett 380:272–280.  https://doi.org/10.1016/j.canlet.2015.10.027CrossRefPubMedPubMedCentralGoogle Scholar
  92. Chiodi I, Mondello C (2012) Telomere-independent functions of telomerase in nuclei, cytoplasm, and mitochondria. Front Oncol 2:133.  https://doi.org/10.3389/fonc.2012.00133CrossRefPubMedPubMedCentralGoogle Scholar
  93. Chivukula RR, Mendell JT (2008) Circular reasoning: microRNAs and cell-cycle control. Trends Biochem Sci 33:474–481.  https://doi.org/10.1016/j.tibs.2008.06.008CrossRefPubMedPubMedCentralGoogle Scholar
  94. Choi SYC, Collins CC, Gout PW, Wang Y (2013) Cancer-generated lactic acid: a regulatory, immunosuppressive metabolite? J Pathol 230:350–355.  https://doi.org/10.1002/path.4218CrossRefPubMedPubMedCentralGoogle Scholar
  95. Choudhry H, Harris AL, McIntyre A (2016) The tumour hypoxia induced non-coding transcriptome. Mol Asp Med 47–48:35–53.  https://doi.org/10.1016/j.mam.2016.01.003CrossRefGoogle Scholar
  96. Chow T-FF, Mankaruos M, Scorilas A et al (2010) The miR-17-92 cluster is over expressed in and has an oncogenic effect on renal cell carcinoma. J Urol 183:743–751.  https://doi.org/10.1016/j.juro.2009.09.086CrossRefPubMedPubMedCentralGoogle Scholar
  97. Chowdhury D, Choi YE, Brault ME (2013) Charity begins at home: non-coding RNA functions in DNA repair. Nat Rev Mol Cell Biol 14:181–189.  https://doi.org/10.1038/nrm3523CrossRefPubMedPubMedCentralGoogle Scholar
  98. Christofk HR, Vander Heiden MG, Harris MH et al (2008) The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452:230–233.  https://doi.org/10.1038/nature06734CrossRefGoogle Scholar
  99. Clarke PGH, Puyal J (2012) Autophagic cell death exists. Autophagy 8:867–869.  https://doi.org/10.4161/auto.20380CrossRefPubMedPubMedCentralGoogle Scholar
  100. Clendening JW, Pandyra A, Boutros PC et al (2010) Dysregulation of the mevalonate pathway promotes transformation. Proc Natl Acad Sci U S A 107:15051–15056.  https://doi.org/10.1073/pnas.0910258107CrossRefPubMedPubMedCentralGoogle Scholar
  101. Cobbs CS, Whisenhunt TR, Wesemann DR et al (2003) Inactivation of wild-type p53 protein function by reactive oxygen and nitrogen species in malignant glioma cells. Cancer Res 63:8670–8673PubMedPubMedCentralGoogle Scholar
  102. Codo P, Weller M, Meister G et al (2014) MicroRNA-mediated down-regulation of NKG2D ligands contributes to glioma immune escape. Oncotarget 5:7651–7662PubMedPubMedCentralCrossRefGoogle Scholar
  103. Cohen SB, Graham ME, Lovrecz GO et al (2007) Protein composition of catalytically active human telomerase from immortal cells. Science 315:1850–1853.  https://doi.org/10.1126/science.1138596CrossRefGoogle Scholar
  104. Colotta F, Allavena P, Sica A et al (2009) Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30:1073–1081.  https://doi.org/10.1093/carcin/bgp127CrossRefPubMedPubMedCentralGoogle Scholar
  105. Comerford SA, Huang Z, Du X et al (2014) Acetate dependence of tumors. Cell 159:1591–1602.  https://doi.org/10.1016/j.cell.2014.11.020CrossRefPubMedPubMedCentralGoogle Scholar
  106. Commisso C, Davidson SM, Soydaner-Azeloglu RG et al (2013) Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497:633–637.  https://doi.org/10.1038/nature12138CrossRefPubMedPubMedCentralGoogle Scholar
  107. Cong Y, Shay JW (2008) Actions of human telomerase beyond telomeres. Cell Res 18:725–732.  https://doi.org/10.1038/cr.2008.74CrossRefPubMedPubMedCentralGoogle Scholar
  108. Conrad M, Sato H (2012) The oxidative stress-inducible cystine/glutamate antiporter, system x (c) (-) : cystine supplier and beyond. Amino Acids 42:231–246.  https://doi.org/10.1007/s00726-011-0867-5CrossRefPubMedPubMedCentralGoogle Scholar
  109. Cook KM, Figg WD (2010) Angiogenesis inhibitors: current strategies and future prospects. CA Cancer J Clin 60:222–243.  https://doi.org/10.3322/caac.20075CrossRefPubMedPubMedCentralGoogle Scholar
  110. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867.  https://doi.org/10.1038/nature01322CrossRefPubMedPubMedCentralGoogle Scholar
  111. Crabtree HG (1929) Observations on the carbohydrate metabolism of tumours. Biochem J 23:536–545PubMedPubMedCentralCrossRefGoogle Scholar
  112. Crosby ME, Kulshreshtha R, Ivan M, Glazer PM (2009) MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res 69:1221–1229.  https://doi.org/10.1158/0008-5472.CAN-08-2516CrossRefPubMedPubMedCentralGoogle Scholar
  113. Csibi A, Fendt S-M, Li C et al (2013) The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell 153:840–854.  https://doi.org/10.1016/j.cell.2013.04.023CrossRefPubMedPubMedCentralGoogle Scholar
  114. Cui M, Wang Y, Sun B et al (2014) MiR-205 modulates abnormal lipid metabolism of hepatoma cells via targeting acyl-CoA synthetase long-chain family member 1 (ACSL1) mRNA. Biochem Biophys Res Commun 444:270–275.  https://doi.org/10.1016/j.bbrc.2014.01.051CrossRefPubMedGoogle Scholar
  115. Currie E, Schulze A, Zechner R et al (2013) Cellular fatty acid metabolism and cancer. Cell Metab 18:153–161.  https://doi.org/10.1016/j.cmet.2013.05.017CrossRefPubMedPubMedCentralGoogle Scholar
  116. Cusanelli E, Chartrand P (2015) Telomeric repeat-containing RNA TERRA: a noncoding RNA connecting telomere biology to genome integrity. Front Genet 6:143.  https://doi.org/10.3389/fgene.2015.00143CrossRefPubMedPubMedCentralGoogle Scholar
  117. d’Adda di Fagagna F (2014) A direct role for small non-coding RNAs in DNA damage response. Trends Cell Biol 24:171–178.  https://doi.org/10.1016/j.tcb.2013.09.008CrossRefPubMedGoogle Scholar
  118. Daniëls VW, Smans K, Royaux I et al (2014) Cancer cells differentially activate and thrive on de novo lipid synthesis pathways in a low-lipid environment. PLoS One 9:e106913.  https://doi.org/10.1371/journal.pone.0106913CrossRefPubMedPubMedCentralGoogle Scholar
  119. Dayaram T, Marriott SJ (2008) Effect of transforming viruses on molecular mechanisms associated with cancer. J Cell Physiol 216:309–314.  https://doi.org/10.1002/jcp.21439CrossRefPubMedPubMedCentralGoogle Scholar
  120. de Gonzalo-Calvo D, López-Vilaró L, Nasarre L et al (2015) Intratumor cholesteryl ester accumulation is associated with human breast cancer proliferation and aggressive potential: a molecular and clinicopathological study. BMC Cancer 15:460.  https://doi.org/10.1186/s12885-015-1469-5CrossRefPubMedPubMedCentralGoogle Scholar
  121. de Lange T (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19:2100–2110.  https://doi.org/10.1101/gad.1346005CrossRefGoogle Scholar
  122. De Vitto H, Pérez-Valencia J, Radosevich JA (2016) Glutamine at focus: versatile roles in cancer. Tumour Biol 37:1541–1558.  https://doi.org/10.1007/s13277-015-4671-9CrossRefPubMedPubMedCentralGoogle Scholar
  123. DeBerardinis RJ, Cheng T (2010) Q’s next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 29:313–324.  https://doi.org/10.1038/onc.2009.358CrossRefPubMedPubMedCentralGoogle Scholar
  124. DeBerardinis RJ, Mancuso A, Daikhin E et al (2007) Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci U S A 104:19345–19350.  https://doi.org/10.1073/pnas.0709747104CrossRefPubMedPubMedCentralGoogle Scholar
  125. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7:11–20.  https://doi.org/10.1016/j.cmet.2007.10.002CrossRefPubMedPubMedCentralGoogle Scholar
  126. DeNardo DG, Johansson M, Coussens LM (2008) Immune cells as mediators of solid tumor metastasis. Cancer Metastasis Rev 27:11–18.  https://doi.org/10.1007/s10555-007-9100-0CrossRefPubMedPubMedCentralGoogle Scholar
  127. DeNardo DG, Andreu P, Coussens LM (2010) Interactions between lymphocytes and myeloid cells regulate pro- versus anti-tumor immunity. Cancer Metastasis Rev 29:309–316.  https://doi.org/10.1007/s10555-010-9223-6CrossRefPubMedPubMedCentralGoogle Scholar
  128. Denchi EL, de Lange T (2007) Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature 448:1068–1071.  https://doi.org/10.1038/nature06065CrossRefPubMedPubMedCentralGoogle Scholar
  129. Deng Y, Chan SS, Chang S (2008) Telomere dysfunction and tumour suppression: the senescence connection. Nat Rev Cancer 8:450–458.  https://doi.org/10.1038/nrc2393CrossRefPubMedPubMedCentralGoogle Scholar
  130. Deng Z, Norseen J, Wiedmer A et al (2009) TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres. Mol Cell 35:403–413.  https://doi.org/10.1016/j.molcel.2009.06.025CrossRefPubMedPubMedCentralGoogle Scholar
  131. Deng Z, Wang Z, Stong N et al (2012) A role for CTCF and cohesin in subtelomere chromatin organization, TERRA transcription, and telomere end protection. EMBO J 31:4165–4178.  https://doi.org/10.1038/emboj.2012.266CrossRefPubMedPubMedCentralGoogle Scholar
  132. Deprez J, Vertommen D, Alessi DR et al (1997) Phosphorylation and activation of heart 6-phosphofructo-2-kinase by protein kinase B and other protein kinases of the insulin signaling cascades. J Biol Chem 272:17269–17275PubMedCrossRefGoogle Scholar
  133. Di Croce L, Raker VA, Corsaro M et al (2002) Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science 295:1079–1082.  https://doi.org/10.1126/science.1065173CrossRefPubMedGoogle Scholar
  134. Di Francesco A, De Pittà C, Moret F et al (2013) The DNA-damage response to γ-radiation is affected by miR-27a in A549 cells. Int J Mol Sci 14:17881–17896.  https://doi.org/10.3390/ijms140917881CrossRefPubMedPubMedCentralGoogle Scholar
  135. Diala I, Wagner N, Magdinier F et al (2013) Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway. EMBO Rep 14:356–363.  https://doi.org/10.1038/embor.2013.16CrossRefPubMedPubMedCentralGoogle Scholar
  136. Dick FA, Rubin SM (2013) Molecular mechanisms underlying RB protein function. Nat Rev Mol Cell Biol 14:297–306.  https://doi.org/10.1038/nrm3567CrossRefPubMedPubMedCentralGoogle Scholar
  137. Dinami R, Petti E, Sestito R et al (2014) microRNAs control the function of telomeres in cancer. RNA Dis.  https://doi.org/10.14800/rd.282
  138. Ding D, Xi P, Zhou J et al (2013a) Human telomerase reverse transcriptase regulates MMP expression independently of telomerase activity via NF-κB-dependent transcription. FASEB J Off Publ Fed Am Soc Exp Biol 27:4375–4383.  https://doi.org/10.1096/fj.13-230904CrossRefGoogle Scholar
  139. Ding D, Zhou J, Wang M, Cong Y-S (2013b) Implications of telomere-independent activities of telomerase reverse transcriptase in human cancer. FEBS J 280:3205–3211.  https://doi.org/10.1111/febs.12258CrossRefPubMedGoogle Scholar
  140. Doksani Y, de Lange T (2014) The role of double-strand break repair pathways at functional and dysfunctional telomeres. Cold Spring Harb Perspect Biol 6:a016576.  https://doi.org/10.1101/cshperspect.a016576CrossRefPubMedPubMedCentralGoogle Scholar
  141. Dötsch V, Bernassola F, Coutandin D et al (2010) p63 and p73, the ancestors of p53. Cold Spring Harb Perspect Biol 2:a004887PubMedPubMedCentralCrossRefGoogle Scholar
  142. Du W, Amarachintha S, Wilson AF, Pang Q (2016a) SCO2 mediates oxidative stress-induced glycolysis to oxidative phosphorylation switch in hematopoietic stem cells. Stem Cells Dayt Ohio 34:960–971.  https://doi.org/10.1002/stem.2260CrossRefGoogle Scholar
  143. Du WW, Yang W, Liu E et al (2016b) Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res 44:2846–2858.  https://doi.org/10.1093/nar/gkw027CrossRefPubMedPubMedCentralGoogle Scholar
  144. Dunn GP, Old LJ, Schreiber RD (2004) The three Es of cancer immunoediting. Annu Rev Immunol 22:329–360.  https://doi.org/10.1146/annurev.immunol.22.012703.104803CrossRefPubMedGoogle Scholar
  145. Duronio RJ, Xiong Y (2013) Signaling pathways that control cell proliferation. Cold Spring Harb Perspect Biol 5:a008904.  https://doi.org/10.1101/cshperspect.a008904CrossRefPubMedPubMedCentralGoogle Scholar
  146. Dürst M, Gissmann L, Ikenberg H, zur Hausen H (1983) A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci U S A 80:3812–3815PubMedPubMedCentralCrossRefGoogle Scholar
  147. Dutton A, O’Neil JD, Milner AE et al (2004) Expression of the cellular FLICE-inhibitory protein (c-FLIP) protects Hodgkin’s lymphoma cells from autonomous Fas-mediated death. Proc Natl Acad Sci U S A 101:6611–6616.  https://doi.org/10.1073/pnas.0400765101CrossRefPubMedPubMedCentralGoogle Scholar
  148. Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:1650–1659.  https://doi.org/10.1056/NEJM198612253152606CrossRefPubMedGoogle Scholar
  149. Eagle H (1955) The minimum vitamin requirements of the L and HeLa cells in tissue culture, the production of specific vitamin deficiencies, and their cure. J Exp Med 102:595–600PubMedPubMedCentralCrossRefGoogle Scholar
  150. Eisengart CA, Mestre JR, Naama HA et al (2000) Prostaglandins regulate melanoma-induced cytokine production in macrophages. Cell Immunol 204:143–149.  https://doi.org/10.1006/cimm.2000.1686CrossRefPubMedPubMedCentralGoogle Scholar
  151. Elinav E, Nowarski R, Thaiss CA et al (2013) Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 13:759–771.  https://doi.org/10.1038/nrc3611CrossRefPubMedGoogle Scholar
  152. Elstrom RL, Bauer DE, Buzzai M et al (2004) Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 64:3892–3899.  https://doi.org/10.1158/0008-5472.CAN-03-2904CrossRefPubMedGoogle Scholar
  153. Eng CH, Yu K, Lucas J et al (2010) Ammonia derived from glutaminolysis is a diffusible regulator of autophagy. Sci Signal 3:ra31.  https://doi.org/10.1126/scisignal.2000911CrossRefPubMedGoogle Scholar
  154. Esquela-Kerscher A, Trang P, Wiggins JF et al (2008) The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle Georget Tex 7:759–764.  https://doi.org/10.4161/cc.7.6.5834CrossRefGoogle Scholar
  155. Estrela JM, Ortega A, Obrador E (2006) Glutathione in cancer biology and therapy. Crit Rev Clin Lab Sci 43:143–181.  https://doi.org/10.1080/10408360500523878CrossRefPubMedGoogle Scholar
  156. Fallarino F, Grohmann U, You S et al (2006) The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol 176:6752–6761PubMedCrossRefGoogle Scholar
  157. Fan J, Hitosugi T, Chung T-W et al (2011) Tyrosine phosphorylation of lactate dehydrogenase A is important for NADH/NAD(+) redox homeostasis in cancer cells. Mol Cell Biol 31:4938–4950.  https://doi.org/10.1128/MCB.06120-11CrossRefPubMedPubMedCentralGoogle Scholar
  158. Fantin VR, St-Pierre J, Leder P (2006) Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 9:425–434.  https://doi.org/10.1016/j.ccr.2006.04.023CrossRefPubMedGoogle Scholar
  159. Farnung BO, Brun CM, Arora R et al (2012) Telomerase efficiently elongates highly transcribing telomeres in human cancer cells. PLoS One 7:e35714.  https://doi.org/10.1371/journal.pone.0035714CrossRefPubMedPubMedCentralGoogle Scholar
  160. Fasanaro P, D’Alessandra Y, Di Stefano V et al (2008) MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem 283:15878–15883.  https://doi.org/10.1074/jbc.M800731200CrossRefPubMedPubMedCentralGoogle Scholar
  161. Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301:89–92PubMedCrossRefGoogle Scholar
  162. Feinberg AP, Gehrke CW, Kuo KC, Ehrlich M (1988) Reduced genomic 5-methylcytosine content in human colonic neoplasia. Cancer Res 48:1159–1161PubMedPubMedCentralGoogle Scholar
  163. Ferrara N, Gerber H-P, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676.  https://doi.org/10.1038/nm0603-669CrossRefPubMedPubMedCentralGoogle Scholar
  164. Feuerhahn S, Iglesias N, Panza A et al (2010) TERRA biogenesis, turnover and implications for function. FEBS Lett 584:3812–3818.  https://doi.org/10.1016/j.febslet.2010.07.032CrossRefPubMedGoogle Scholar
  165. Filella X, Molina R, Jo J et al (1991) Serum phosphohexose isomerase activities in patients with colorectal cancer. Tumour Biol 12:360–367PubMedCrossRefGoogle Scholar
  166. Fischer K, Hoffmann P, Voelkl S et al (2007) Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood 109:3812–3819.  https://doi.org/10.1182/blood-2006-07-035972CrossRefPubMedGoogle Scholar
  167. Flynn RL, Centore RC, O’Sullivan RJ et al (2011) TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature 471:532–536.  https://doi.org/10.1038/nature09772CrossRefPubMedPubMedCentralGoogle Scholar
  168. Flynn RL, Cox KE, Jeitany M et al (2015) Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors. Science 347:273–277.  https://doi.org/10.1126/science.1257216CrossRefPubMedPubMedCentralGoogle Scholar
  169. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186.  https://doi.org/10.1056/NEJM197111182852108CrossRefPubMedGoogle Scholar
  170. Folmes CDL, Nelson TJ, Martinez-Fernandez A et al (2011) Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming. Cell Metab 14:264–271.  https://doi.org/10.1016/j.cmet.2011.06.011CrossRefPubMedPubMedCentralGoogle Scholar
  171. Fornaro M, Plescia J, Chheang S et al (2003) Fibronectin protects prostate cancer cells from tumor necrosis factor-alpha-induced apoptosis via the AKT/survivin pathway. J Biol Chem 278:50402–50411.  https://doi.org/10.1074/jbc.M307627200CrossRefPubMedGoogle Scholar
  172. Frankel B, Longo SL, Canute GW (2000) Soluble Fas-ligand (sFasL) in human astrocytoma cyst fluid is cytotoxic to T-cells: another potential means of immune evasion. J Neuro-Oncol 48:21–26CrossRefGoogle Scholar
  173. Freed-Pastor WA, Mizuno H, Zhao X et al (2012) Mutant p53 disrupts mammary tissue architecture via the mevalonate pathway. Cell 148:244–258.  https://doi.org/10.1016/j.cell.2011.12.017CrossRefPubMedPubMedCentralGoogle Scholar
  174. Fujita Y, Yagishita S, Hagiwara K et al (2015) The clinical relevance of the miR-197/CKS1B/STAT3-mediated PD-L1 network in chemoresistant non-small-cell lung cancer. Mol Ther J Am Soc Gene Ther 23:717–727.  https://doi.org/10.1038/mt.2015.10CrossRefGoogle Scholar
  175. Fukuda R, Zhang H, Kim J et al (2007) HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell 129:111–122.  https://doi.org/10.1016/j.cell.2007.01.047CrossRefPubMedPubMedCentralGoogle Scholar
  176. Furuta E, Pai SK, Zhan R et al (2008) Fatty acid synthase gene is up-regulated by hypoxia via activation of Akt and sterol regulatory element binding protein-1. Cancer Res 68:1003–1011.  https://doi.org/10.1158/0008-5472.CAN-07-2489CrossRefPubMedPubMedCentralGoogle Scholar
  177. Gabrilovich DI, Corak J, Ciernik IF et al (1997) Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res 3:483–490Google Scholar
  178. Gajjar M, Candeias MM, Malbert-Colas L et al (2012) The p53 mRNA-Mdm2 interaction controls Mdm2 nuclear trafficking and is required for p53 activation following DNA damage. Cancer Cell 21:25–35.  https://doi.org/10.1016/j.ccr.2011.11.016CrossRefPubMedPubMedCentralGoogle Scholar
  179. Gallach S, Calabuig-Fariñas S, Jantus-Lewintre E, Camps C (2014) MicroRNAs: promising new antiangiogenic targets in cancer. Biomed Res Int 2014:878450.  https://doi.org/10.1155/2014/878450CrossRefPubMedPubMedCentralGoogle Scholar
  180. Gao P, Tchernyshyov I, Chang T-C et al (2009) c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458:762–765.  https://doi.org/10.1038/nature07823CrossRefPubMedPubMedCentralGoogle Scholar
  181. Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4:891–899.  https://doi.org/10.1038/nrc1478CrossRefPubMedPubMedCentralGoogle Scholar
  182. Gebert D, Rosenkranz D (2015) RNA-based regulation of transposon expression. Wiley Interdiscip Rev RNA 6:687–708.  https://doi.org/10.1002/wrna.1310CrossRefPubMedPubMedCentralGoogle Scholar
  183. Gee HE, Ivan C, Calin GA, Ivan M (2014) HypoxamiRs and cancer: from biology to targeted therapy. Antioxid Redox Signal 21:1220–1238.  https://doi.org/10.1089/ars.2013.5639CrossRefPubMedPubMedCentralGoogle Scholar
  184. Gentric G, Mieulet V, Mechta-Grigoriou F (2017) Heterogeneity in cancer metabolism: new concepts in an old field. Antioxid Redox Signal 26:462–485.  https://doi.org/10.1089/ars.2016.6750CrossRefPubMedPubMedCentralGoogle Scholar
  185. Ghosh G, Subramanian IV, Adhikari N et al (2010) Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-α isoforms and promotes angiogenesis. J Clin Invest 120:4141–4154.  https://doi.org/10.1172/JCI42980CrossRefPubMedPubMedCentralGoogle Scholar
  186. Ghosh A, Saginc G, Leow SC et al (2012) Telomerase directly regulates NF-κB-dependent transcription. Nat Cell Biol 14:1270–1281.  https://doi.org/10.1038/ncb2621CrossRefPubMedPubMedCentralGoogle Scholar
  187. Gil J, Peters G (2006) Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all. Nat Rev Mol Cell Biol 7:667–677.  https://doi.org/10.1038/nrm1987CrossRefPubMedPubMedCentralGoogle Scholar
  188. Giordano A, Calvani M, Petillo O et al (2005) tBid induces alterations of mitochondrial fatty acid oxidation flux by malonyl-CoA-independent inhibition of carnitine palmitoyltransferase-1. Cell Death Differ 12:603–613.  https://doi.org/10.1038/sj.cdd.4401636CrossRefPubMedPubMedCentralGoogle Scholar
  189. Godlewski J, Nowicki MO, Bronisz A et al (2010) MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells. Mol Cell 37:620–632.  https://doi.org/10.1016/j.molcel.2010.02.018CrossRefPubMedPubMedCentralGoogle Scholar
  190. Gómez-Maldonado L, Tiana M, Roche O et al (2015) EFNA3 long noncoding RNAs induced by hypoxia promote metastatic dissemination. Oncogene 34:2609–2620.  https://doi.org/10.1038/onc.2014.200CrossRefPubMedPubMedCentralGoogle Scholar
  191. Gong A-Y, Zhou R, Hu G et al (2009) MicroRNA-513 regulates B7-H1 translation and is involved in IFN-gamma-induced B7-H1 expression in cholangiocytes. J Immunol 182:1325–1333PubMedPubMedCentralCrossRefGoogle Scholar
  192. Gonzalez-Perez A, Jene-Sanz A, Lopez-Bigas N (2013) The mutational landscape of chromatin regulatory factors across 4,623 tumor samples. Genome Biol 14:r106.  https://doi.org/10.1186/gb-2013-14-9-r106CrossRefPubMedPubMedCentralGoogle Scholar
  193. Goodwin ML, Gladden LB, Nijsten MWN, Jones KB (2014) Lactate and cancer: revisiting the warburg effect in an era of lactate shuttling. Front Nutr 1:27.  https://doi.org/10.3389/fnut.2014.00027CrossRefPubMedPubMedCentralGoogle Scholar
  194. Gottfried E, Kunz-Schughart LA, Ebner S et al (2006) Tumor-derived lactic acid modulates dendritic cell activation and antigen expression. Blood 107:2013–2021.  https://doi.org/10.1182/blood-2005-05-1795CrossRefPubMedPubMedCentralGoogle Scholar
  195. Gozuacik D, Akkoc Y, Ozturk DG, Kocak M (2017) Autophagy-Regulating microRNAs and Cancer. Front Oncol 7:65.  https://doi.org/10.3389/fonc.2017.00065CrossRefPubMedPubMedCentralGoogle Scholar
  196. Graf H, Jüngst C, Straub G et al (2008) Chemoembolization combined with pravastatin improves survival in patients with hepatocellular carcinoma. Digestion 78:34–38.  https://doi.org/10.1159/000156702CrossRefPubMedPubMedCentralGoogle Scholar
  197. Grivennikov SI, Karin M (2010) Inflammation and oncogenesis: a vicious connection. Curr Opin Genet Dev 20:65–71.  https://doi.org/10.1016/j.gde.2009.11.004CrossRefPubMedPubMedCentralGoogle Scholar
  198. Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140:883–899.  https://doi.org/10.1016/j.cell.2010.01.025CrossRefPubMedPubMedCentralGoogle Scholar
  199. Groh V, Wu J, Yee C, Spies T (2002) Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 419:734–738.  https://doi.org/10.1038/nature01112CrossRefPubMedPubMedCentralGoogle Scholar
  200. Groves AM, Win T, Haim SB, Ell PJ (2007) Non-[18F]FDG PET in clinical oncology. Lancet Oncol 8:822–830.  https://doi.org/10.1016/S1470-2045(07)70274-7CrossRefPubMedPubMedCentralGoogle Scholar
  201. Guan Z, Song B, Liu F et al (2015) TGF-β induces HLA-G expression through inhibiting miR-152 in gastric cancer cells. J Biomed Sci 22:107.  https://doi.org/10.1186/s12929-015-0177-4CrossRefPubMedPubMedCentralGoogle Scholar
  202. Guertin DA, Sabatini DM (2007) Defining the role of mTOR in cancer. Cancer Cell 12(1):9–22PubMedCrossRefPubMedCentralGoogle Scholar
  203. Guillaumond F, Bidaut G, Ouaissi M et al (2015) Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma. Proc Natl Acad Sci U S A 112:2473–2478.  https://doi.org/10.1073/pnas.1421601112CrossRefPubMedPubMedCentralGoogle Scholar
  204. Gundara JS, Zhao J, Robinson BG, Sidhu SB (2012) Oncophagy: harnessing regulation of autophagy in cancer therapy. Endocr Relat Cancer 19:R281–R295.  https://doi.org/10.1530/ERC-12-0325CrossRefPubMedPubMedCentralGoogle Scholar
  205. Guo C, Sah JF, Beard L et al (2008) The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers. Genes Chromosom Cancer 47:939–946.  https://doi.org/10.1002/gcc.20596CrossRefPubMedPubMedCentralGoogle Scholar
  206. Guo D, Reinitz F, Youssef M et al (2011) An LXR agonist promotes glioblastoma cell death through inhibition of an EGFR/AKT/SREBP-1/LDLR-dependent pathway. Cancer Discov 1:442–456.  https://doi.org/10.1158/2159-8290.CD-11-0102CrossRefPubMedPubMedCentralGoogle Scholar
  207. Guo C, Liu S, Sun M-Z (2013) Novel insight into the role of GAPDH playing in tumor. Clin Transl Oncol Off Publ Fed Span Oncol Soc Natl Cancer Inst Mex 15:167–172.  https://doi.org/10.1007/s12094-012-0924-xCrossRefGoogle Scholar
  208. Guo P, Lan J, Ge J et al (2014) MiR-26a enhances the radiosensitivity of glioblastoma multiforme cells through targeting of ataxia-telangiectasia mutated. Exp Cell Res 320:200–208.  https://doi.org/10.1016/j.yexcr.2013.10.020CrossRefPubMedPubMedCentralGoogle Scholar
  209. Guo W, Tan W, Liu S et al (2015) MiR-570 inhibited the cell proliferation and invasion through directly targeting B7-H1 in hepatocellular carcinoma. Tumour Biol 36:9049–9057.  https://doi.org/10.1007/s13277-015-3644-3CrossRefPubMedPubMedCentralGoogle Scholar
  210. Guppy M, Leedman P, Zu X, Russell V (2002) Contribution by different fuels and metabolic pathways to the total ATP turnover of proliferating MCF-7 breast cancer cells. Biochem J 364:309–315PubMedPubMedCentralCrossRefGoogle Scholar
  211. Gutschner T, Diederichs S (2012) The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol 9:703–719.  https://doi.org/10.4161/rna.20481CrossRefPubMedPubMedCentralGoogle Scholar
  212. Hadjiargyrou M, Delihas N (2013) The intertwining of transposable elements and non-coding RNAs. Int J Mol Sci 14:13307–13328.  https://doi.org/10.3390/ijms140713307CrossRefPubMedPubMedCentralGoogle Scholar
  213. Hagan JP, Piskounova E, Gregory RI (2009) Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells. Nat Struct Mol Biol 16:1021–1025.  https://doi.org/10.1038/nsmb.1676CrossRefPubMedPubMedCentralGoogle Scholar
  214. Hagerling C, Casbon A-J, Werb Z (2015) Balancing the innate immune system in tumor development. Trends Cell Biol 25:214–220.  https://doi.org/10.1016/j.tcb.2014.11.001CrossRefPubMedPubMedCentralGoogle Scholar
  215. Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364PubMedCrossRefPubMedCentralGoogle Scholar
  216. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674.  https://doi.org/10.1016/j.cell.2011.02.013CrossRefGoogle Scholar
  217. Hanai J, Doro N, Sasaki AT et al (2012) Inhibition of lung cancer growth: ATP citrate lyase knockdown and statin treatment leads to dual blockade of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/AKT pathways. J Cell Physiol 227:1709–1720.  https://doi.org/10.1002/jcp.22895CrossRefPubMedPubMedCentralGoogle Scholar
  218. Harada K, Baba Y, Ishimoto T et al (2015) LINE-1 methylation level and patient prognosis in a database of 208 hepatocellular carcinomas. Ann Surg Oncol 22:1280–1287.  https://doi.org/10.1245/s10434-014-4134-3CrossRefPubMedPubMedCentralGoogle Scholar
  219. Hardee ME, Dewhirst MW, Agarwal N, Sorg BS (2009) Novel imaging provides new insights into mechanisms of oxygen transport in tumors. Curr Mol Med 9:435–441PubMedPubMedCentralCrossRefGoogle Scholar
  220. Hardie DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8:774–785.  https://doi.org/10.1038/nrm2249CrossRefGoogle Scholar
  221. Hardie DG (2011) AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev 25:1895–1908.  https://doi.org/10.1101/gad.17420111CrossRefPubMedPubMedCentralGoogle Scholar
  222. Hassanein M, Hoeksema MD, Shiota M et al (2013) SLC1A5 mediates glutamine transport required for lung cancer cell growth and survival. Clin Cancer Res Off J Am Assoc Cancer Res 19:560–570.  https://doi.org/10.1158/1078-0432.CCR-12-2334CrossRefGoogle Scholar
  223. Hatziapostolou M, Iliopoulos D (2011) Epigenetic aberrations during oncogenesis. Cell Mol Life Sci 68:1681–1702.  https://doi.org/10.1007/s00018-010-0624-zCrossRefPubMedPubMedCentralGoogle Scholar
  224. Hatziapostolou M, Polytarchou C, Iliopoulos D (2013) miRNAs link metabolic reprogramming to oncogenesis. Trends Endocrinol Metab 24:361–373.  https://doi.org/10.1016/j.tem.2013.03.002CrossRefPubMedPubMedCentralGoogle Scholar
  225. He C, Klionsky DJ (2009) Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 43:67–93.  https://doi.org/10.1146/annurev-genet-102808-114910CrossRefPubMedPubMedCentralGoogle Scholar
  226. He L, He X, Lim LP et al (2007) A microRNA component of the p53 tumour suppressor network. Nature 447:1130–1134.  https://doi.org/10.1038/nature05939CrossRefPubMedPubMedCentralGoogle Scholar
  227. Hensley CT, Wasti AT, DeBerardinis RJ (2013) Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin Invest 123:3678–3684.  https://doi.org/10.1172/JCI69600CrossRefPubMedPubMedCentralGoogle Scholar
  228. Heo I, Joo C, Kim Y-K et al (2009) TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. Cell 138:696–708.  https://doi.org/10.1016/j.cell.2009.08.002CrossRefGoogle Scholar
  229. Hermanson M, Funa K, Hartman M et al (1992) Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops. Cancer Res 52:3213–3219PubMedPubMedCentralGoogle Scholar
  230. Hicklin DJ, Marincola FM, Ferrone S (1999) HLA class I antigen downregulation in human cancers: T-cell immunotherapy revives an old story. Mol Med Today 5:178–186PubMedCrossRefPubMedCentralGoogle Scholar
  231. Higashimoto K, Soejima H, Saito T et al (2006) Imprinting disruption of the CDKN1C/KCNQ1OT1 domain: the molecular mechanisms causing Beckwith-Wiedemann syndrome and cancer. Cytogenet Genome Res 113:306–312.  https://doi.org/10.1159/000090846CrossRefPubMedGoogle Scholar
  232. Hirschhaeuser F, Sattler UGA, Mueller-Klieser W (2011) Lactate: a metabolic key player in cancer. Cancer Res 71:6921–6925.  https://doi.org/10.1158/0008-5472.CAN-11-1457CrossRefPubMedGoogle Scholar
  233. Hmadcha A, Bedoya FJ, Sobrino F, Pintado E (1999) Methylation-dependent gene silencing induced by interleukin 1beta via nitric oxide production. J Exp Med 190:1595–1604PubMedPubMedCentralCrossRefGoogle Scholar
  234. Hodge DR, Peng B, Cherry JC et al (2005) Interleukin 6 supports the maintenance of p53 tumor suppressor gene promoter methylation. Cancer Res 65:4673–4682.  https://doi.org/10.1158/0008-5472.CAN-04-3589CrossRefPubMedGoogle Scholar
  235. Hoffmeyer K, Raggioli A, Rudloff S et al (2012) Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells. Science 336:1549–1554.  https://doi.org/10.1126/science.1218370CrossRefPubMedGoogle Scholar
  236. Hofseth LJ, Khan MA, Ambrose M et al (2003) The adaptive imbalance in base excision-repair enzymes generates microsatellite instability in chronic inflammation. J Clin Invest 112:1887–1894.  https://doi.org/10.1172/JCI19757CrossRefPubMedPubMedCentralGoogle Scholar
  237. Hollander MC, Alamo I, Fornace AJ (1996) A novel DNA damage-inducible transcript, gadd7, inhibits cell growth, but lacks a protein product. Nucleic Acids Res 24:1589–1593PubMedPubMedCentralCrossRefGoogle Scholar
  238. Hollander MC, Blumenthal GM, Dennis PA (2011) PTEN loss in the continuum of common cancers, rare syndromes and mouse models. Nat Rev Cancer 11:289–301.  https://doi.org/10.1038/nrc3037CrossRefPubMedGoogle Scholar
  239. Hollingworth R, Grand RJ (2015) Modulation of DNA damage and repair pathways by human tumour viruses. Viruses 7:2542–2591.  https://doi.org/10.3390/v7052542CrossRefPubMedPubMedCentralGoogle Scholar
  240. Honda R, Yasuda H (1999) Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53. EMBO J 18:22–27.  https://doi.org/10.1093/emboj/18.1.22CrossRefPubMedPubMedCentralGoogle Scholar
  241. Hopperton KE, Duncan RE, Bazinet RP, Archer MC (2014) Fatty acid synthase plays a role in cancer metabolism beyond providing fatty acids for phospholipid synthesis or sustaining elevations in glycolytic activity. Exp Cell Res 320:302–310.  https://doi.org/10.1016/j.yexcr.2013.10.016CrossRefPubMedGoogle Scholar
  242. Horton JD, Goldstein JL, Brown MS (2002) SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109:1125–1131.  https://doi.org/10.1172/JCI15593CrossRefPubMedPubMedCentralGoogle Scholar
  243. Hrdlicková R, Nehyba J, Bose HR (2012) Alternatively spliced telomerase reverse transcriptase variants lacking telomerase activity stimulate cell proliferation. Mol Cell Biol 32:4283–4296.  https://doi.org/10.1128/MCB.00550-12CrossRefPubMedPubMedCentralGoogle Scholar
  244. Hrdličková R, Nehyba J, Bargmann W, Bose HR (2014) Multiple tumor suppressor microRNAs regulate telomerase and TCF7, an important transcriptional regulator of the Wnt pathway. PLoS One 9:e86990.  https://doi.org/10.1371/journal.pone.0086990CrossRefPubMedPubMedCentralGoogle Scholar
  245. Hsu T-L, Chang Y-C, Chen S-J et al (2002) Modulation of dendritic cell differentiation and maturation by decoy receptor 3. J Immunol 168:4846–4853PubMedCrossRefPubMedCentralGoogle Scholar
  246. Hu H, Du L, Nagabayashi G et al (2010) ATM is down-regulated by N-Myc-regulated microRNA-421. Proc Natl Acad Sci U S A 107:1506–1511.  https://doi.org/10.1073/pnas.0907763107CrossRefPubMedPubMedCentralGoogle Scholar
  247. Hua Z, Lv Q, Ye W et al (2006) MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS One 1:e116.  https://doi.org/10.1371/journal.pone.0000116CrossRefPubMedPubMedCentralGoogle Scholar
  248. Huang S, Apasov S, Koshiba M, Sitkovsky M (1997) Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion. Blood 90:1600–1610PubMedPubMedCentralGoogle Scholar
  249. Huang X, Le Q-T, Giaccia AJ (2010) MiR-210--micromanager of the hypoxia pathway. Trends Mol Med 16:230–237.  https://doi.org/10.1016/j.molmed.2010.03.004CrossRefPubMedPubMedCentralGoogle Scholar
  250. Huang L, Luo J, Cai Q et al (2011) MicroRNA-125b suppresses the development of bladder cancer by targeting E2F3. Int J Cancer 128:1758–1769.  https://doi.org/10.1002/ijc.25509CrossRefPubMedPubMedCentralGoogle Scholar
  251. Huang F, Zhao Y, Zhao J et al (2014) Upregulated SLC1A5 promotes cell growth and survival in colorectal cancer. Int J Clin Exp Pathol 7:6006–6014PubMedPubMedCentralGoogle Scholar
  252. Hudson JD, Shoaibi MA, Maestro R et al (1999) A proinflammatory cytokine inhibits p53 tumor suppressor activity. J Exp Med 190:1375–1382PubMedPubMedCentralCrossRefGoogle Scholar
  253. Hussain SP, Harris CC (2007) Inflammation and cancer: an ancient link with novel potentials. Int J Cancer 121:2373–2380.  https://doi.org/10.1002/ijc.23173CrossRefPubMedGoogle Scholar
  254. Hwang HC, Clurman BE (2005) Cyclin E in normal and neoplastic cell cycles. Oncogene 24:2776–2786.  https://doi.org/10.1038/sj.onc.1208613CrossRefPubMedPubMedCentralGoogle Scholar
  255. Iaquinta PJ, Lees JA (2007) Life and death decisions by the E2F transcription factors. Curr Opin Cell Biol 19:649–657.  https://doi.org/10.1016/j.ceb.2007.10.006CrossRefPubMedPubMedCentralGoogle Scholar
  256. Ibrahim EC, Aractingi S, Allory Y et al (2004) Analysis of HLA antigen expression in benign and malignant melanocytic lesions reveals that upregulation of HLA-G expression correlates with malignant transformation, high inflammatory infiltration and HLA-A1 genotype. Int J Cancer 108:243–250.  https://doi.org/10.1002/ijc.11456CrossRefPubMedGoogle Scholar
  257. Ichimura A, Ruike Y, Terasawa K, Tsujimoto G (2011) miRNAs and regulation of cell signaling. FEBS J 278:1610–1618.  https://doi.org/10.1111/j.1742-4658.2011.08087.xCrossRefPubMedGoogle Scholar
  258. Iezzi S, Fanciulli M (2015) Discovering Che-1/AATF: a new attractive target for cancer therapy. Front Genet.  https://doi.org/10.3389/fgene.2015.00141
  259. Iliopoulos D, Jaeger SA, Hirsch HA et al (2010) STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell 39:493–506.  https://doi.org/10.1016/j.molcel.2010.07.023CrossRefPubMedPubMedCentralGoogle Scholar
  260. Inoki K, Li Y, Zhu T et al (2002) TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 4:648–657.  https://doi.org/10.1038/ncb839CrossRefPubMedGoogle Scholar
  261. Jacobs JFM, Nierkens S, Figdor CG et al (2012) Regulatory T cells in melanoma: the final hurdle towards effective immunotherapy? Lancet Oncol 13:e32–e42.  https://doi.org/10.1016/S1470-2045(11)70155-3CrossRefPubMedGoogle Scholar
  262. Jafri MA, Ansari SA, Alqahtani MH, Shay JW (2016) Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies. Genome Med 8:69.  https://doi.org/10.1186/s13073-016-0324-xCrossRefPubMedPubMedCentralGoogle Scholar
  263. Jain MV, Paczulla AM, Klonisch T et al (2013) Interconnections between apoptotic, autophagic and necrotic pathways: implications for cancer therapy development. J Cell Mol Med 17:12–29.  https://doi.org/10.1111/jcmm.12001CrossRefPubMedPubMedCentralGoogle Scholar
  264. Jiang X, Sun Q, Li H et al (2014) The role of phosphoglycerate mutase 1 in tumor aerobic glycolysis and its potential therapeutic implications. Int J Cancer 135:1991–1996.  https://doi.org/10.1002/ijc.28637CrossRefPubMedGoogle Scholar
  265. Jiang C, Fang X, Zhang H et al (2017a) Triptolide inhibits the growth of osteosarcoma by regulating microRNA-181a via targeting PTEN gene in vivo and vitro. Tumour Biol 39:1010428317697556.  https://doi.org/10.1177/1010428317697556CrossRefPubMedGoogle Scholar
  266. Jiang R, Tang J, Chen Y et al (2017b) The long noncoding RNA lnc-EGFR stimulates T-regulatory cells differentiation thus promoting hepatocellular carcinoma immune evasion. Nat Commun 8:15129.  https://doi.org/10.1038/ncomms15129CrossRefPubMedPubMedCentralGoogle Scholar
  267. Jin L-H, Wei C (2014) Role of microRNAs in the Warburg effect and mitochondrial metabolism in cancer. Asian Pac J Cancer Prev 15:7015–7019PubMedCrossRefGoogle Scholar
  268. Johnsen AK, Templeton DJ, Sy M, Harding CV (1999) Deficiency of transporter for antigen presentation (TAP) in tumor cells allows evasion of immune surveillance and increases tumorigenesis. J Immunol 163:4224–4231PubMedGoogle Scholar
  269. Johnson SM, Grosshans H, Shingara J et al (2005) RAS is regulated by the let-7 microRNA family. Cell 120:635–647.  https://doi.org/10.1016/j.cell.2005.01.014CrossRefPubMedGoogle Scholar
  270. Johnson CD, Esquela-Kerscher A, Stefani G et al (2007) The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res 67:7713–7722.  https://doi.org/10.1158/0008-5472.CAN-07-1083CrossRefPubMedGoogle Scholar
  271. Johnsson P, Ackley A, Vidarsdottir L et al (2013) A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells. Nat Struct Mol Biol 20:440–446.  https://doi.org/10.1038/nsmb.2516CrossRefPubMedPubMedCentralGoogle Scholar
  272. Jones RG, Thompson CB (2009) Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev 23:537–548.  https://doi.org/10.1101/gad.1756509CrossRefPubMedPubMedCentralGoogle Scholar
  273. Justus CR, Sanderlin EJ, Yang LV (2015) Molecular connections between cancer cell metabolism and the tumor microenvironment. Int J Mol Sci 16:11055–11086.  https://doi.org/10.3390/ijms160511055CrossRefPubMedPubMedCentralGoogle Scholar
  274. Kaelin WG, Ratcliffe PJ (2008) Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 30:393–402.  https://doi.org/10.1016/j.molcel.2008.04.009CrossRefPubMedPubMedCentralGoogle Scholar
  275. Kahn BB, Alquier T, Carling D, Hardie DG (2005) AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1:15–25.  https://doi.org/10.1016/j.cmet.2004.12.003CrossRefPubMedGoogle Scholar
  276. Kamphorst JJ, Cross JR, Fan J et al (2013) Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci U S A 110:8882–8887.  https://doi.org/10.1073/pnas.1307237110CrossRefPubMedPubMedCentralGoogle Scholar
  277. Kaplan DH, Shankaran V, Dighe AS et al (1998) Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci U S A 95:7556–7561PubMedPubMedCentralCrossRefGoogle Scholar
  278. Karar J, Maity A (2011) PI3K/AKT/mTOR pathway in angiogenesis. Front Mol Neurosci 4:51.  https://doi.org/10.3389/fnmol.2011.00051CrossRefPubMedPubMedCentralGoogle Scholar
  279. Karin M, Greten FR (2005) NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 5:749–759.  https://doi.org/10.1038/nri1703CrossRefPubMedGoogle Scholar
  280. Kase H, Aoki Y, Tanaka K (2003) Fas ligand expression in cervical adenocarcinoma: relevance to lymph node metastasis and tumor progression. Gynecol Oncol 90:70–74PubMedCrossRefGoogle Scholar
  281. Kasiappan R, Shen Z, Tse AK-W et al (2012) 1,25-Dihydroxyvitamin D3 suppresses telomerase expression and human cancer growth through microRNA-498. J Biol Chem 287:41297–41309.  https://doi.org/10.1074/jbc.M112.407189CrossRefPubMedPubMedCentralGoogle Scholar
  282. Kato M, Putta S, Wang M et al (2009) TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat Cell Biol 11:881–889.  https://doi.org/10.1038/ncb1897CrossRefPubMedPubMedCentralGoogle Scholar
  283. Kaul D (2016) AATF RNome: cellular antiviral armour. J Antivir Antiretrovir 8:1–3.  https://doi.org/10.4172/jaa.1000131CrossRefGoogle Scholar
  284. Kazerounian S, Yee KO, Lawler J (2008) Thrombospondins in cancer. Cell Mol Life Sci 65:700–712.  https://doi.org/10.1007/s00018-007-7486-zCrossRefPubMedPubMedCentralGoogle Scholar
  285. Kefas B, Godlewski J, Comeau L et al (2008) microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma. Cancer Res 68:3566–3572.  https://doi.org/10.1158/0008-5472.CAN-07-6639CrossRefPubMedGoogle Scholar
  286. Keniry A, Oxley D, Monnier P et al (2012) The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r. Nat Cell Biol 14:659–665.  https://doi.org/10.1038/ncb2521CrossRefPubMedPubMedCentralGoogle Scholar
  287. Kessler R, Bleichert F, Warnke J-P, Eschrich K (2008) 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) is up-regulated in high-grade astrocytomas. J Neuro-Oncol 86:257–264.  https://doi.org/10.1007/s11060-007-9471-7CrossRefGoogle Scholar
  288. Khanduja JS, Calvo IA, Joh RI et al (2016) Nuclear noncoding rnas and genome stability. Mol Cell 63:7–20.  https://doi.org/10.1016/j.molcel.2016.06.011CrossRefPubMedPubMedCentralGoogle Scholar
  289. Khatri S, Yepiskoposyan H, Gallo CA et al (2010) FOXO3a regulates glycolysis via transcriptional control of tumor suppressor TSC1. J Biol Chem 285:15960–15965.  https://doi.org/10.1074/jbc.M110.121871CrossRefPubMedPubMedCentralGoogle Scholar
  290. Kikuchi M, Kuroki S, Kayama M et al (2012) Protease activity of procaspase-8 is essential for cell survival by inhibiting both apoptotic and nonapoptotic cell death dependent on receptor-interacting protein kinase 1 (RIP1) and RIP3. J Biol Chem 287:41165–41173.  https://doi.org/10.1074/jbc.M112.419747CrossRefPubMedPubMedCentralGoogle Scholar
  291. Kim J-W, Dang CV (2005) Multifaceted roles of glycolytic enzymes. Trends Biochem Sci 30:142–150.  https://doi.org/10.1016/j.tibs.2005.01.005CrossRefPubMedGoogle Scholar
  292. Kim J, Dang CV (2006) Cancer’s molecular sweet tooth and the Warburg effect. Cancer Res 66:8927–8930.  https://doi.org/10.1158/0008-5472.CAN-06-1501CrossRefPubMedGoogle Scholar
  293. Kim B, Ha M, Loeff L et al (2015) TUT7 controls the fate of precursor microRNAs by using three different uridylation mechanisms. EMBO J 34:1801–1815.  https://doi.org/10.15252/embj.201590931CrossRefPubMedPubMedCentralGoogle Scholar
  294. Kitagawa M, Kitagawa K, Kotake Y et al (2013) Cell cycle regulation by long non-coding RNAs. Cell Mol Life Sci 70:4785–4794.  https://doi.org/10.1007/s00018-013-1423-0CrossRefPubMedPubMedCentralGoogle Scholar
  295. Knobloch M, Braun SMG, Zurkirchen L et al (2013) Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis. Nature 493:226–230.  https://doi.org/10.1038/nature11689CrossRefPubMedGoogle Scholar
  296. Kohn AD, Summers SA, Birnbaum MJ, Roth RA (1996) Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation. J Biol Chem 271:31372–31378PubMedCrossRefGoogle Scholar
  297. Konstantinopoulos PA, Karamouzis MV, Papavassiliou AG (2007) Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets. Nat Rev Drug Discov 6:541–555.  https://doi.org/10.1038/nrd2221CrossRefPubMedPubMedCentralGoogle Scholar
  298. Korc M, Friesel RE (2009) The role of fibroblast growth factors in tumor growth. Curr Cancer Drug Targets 9:639–651PubMedPubMedCentralCrossRefGoogle Scholar
  299. Kornblau SM, Banker DE, Stirewalt D et al (2007) Blockade of adaptive defensive changes in cholesterol uptake and synthesis in AML by the addition of pravastatin to idarubicin + high-dose Ara-C: a phase 1 study. Blood 109:2999–3006.  https://doi.org/10.1182/blood-2006-08-044446CrossRefPubMedPubMedCentralGoogle Scholar
  300. Kosaka N, Iguchi H, Hagiwara K et al (2013) Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis. J Biol Chem 288:10849–10859.  https://doi.org/10.1074/jbc.M112.446831CrossRefPubMedPubMedCentralGoogle Scholar
  301. Kotake Y, Nakagawa T, Kitagawa K et al (2011) Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene 30:1956–1962.  https://doi.org/10.1038/onc.2010.568CrossRefPubMedPubMedCentralGoogle Scholar
  302. Kovacević Z (1971) The pathway of glutamine and glutamate oxidation in isolated mitochondria from mammalian cells. Biochem J 125:757–763PubMedPubMedCentralCrossRefGoogle Scholar
  303. Koyama S, Koike N, Adachi S (2002) Expression of TNF-related apoptosis-inducing ligand (TRAIL) and its receptors in gastric carcinoma and tumor-infiltrating lymphocytes: a possible mechanism of immune evasion of the tumor. J Cancer Res Clin Oncol 128:73–79.  https://doi.org/10.1007/s004320100292CrossRefPubMedPubMedCentralGoogle Scholar
  304. Krebs HA (1935) Metabolism of amino-acids: The synthesis of glutamine from glutamic acid and ammonia, and the enzymic hydrolysis of glutamine in animal tissues. Biochem J 29:1951–1969PubMedPubMedCentralCrossRefGoogle Scholar
  305. Krycer JR, Sharpe LJ, Luu W, Brown AJ (2010) The Akt-SREBP nexus: cell signaling meets lipid metabolism. Trends Endocrinol Metab 21:268–276.  https://doi.org/10.1016/j.tem.2010.01.001CrossRefPubMedPubMedCentralGoogle Scholar
  306. Kuhajda FP, Jenner K, Wood FD et al (1994) Fatty acid synthesis: a potential selective target for antineoplastic therapy. Proc Natl Acad Sci U S A 91:6379–6383PubMedPubMedCentralCrossRefGoogle Scholar
  307. Kumar MS, Erkeland SJ, Pester RE et al (2008) Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci U S A 105:3903–3908.  https://doi.org/10.1073/pnas.0712321105CrossRefPubMedPubMedCentralGoogle Scholar
  308. Kundu JK, Surh Y-J (2008) Inflammation: gearing the journey to cancer. Mutat Res 659:15–30.  https://doi.org/10.1016/j.mrrev.2008.03.002CrossRefPubMedPubMedCentralGoogle Scholar
  309. Kurokawa R (2011) Promoter-associated long noncoding RNAs repress transcription through a RNA binding protein TLS. Adv Exp Med Biol 722:196–208.  https://doi.org/10.1007/978-1-4614-0332-6_12CrossRefPubMedPubMedCentralGoogle Scholar
  310. Kutty RK, Nagineni CN, Samuel W et al (2010) Inflammatory cytokines regulate microRNA-155 expression in human retinal pigment epithelial cells by activating JAK/STAT pathway. Biochem Biophys Res Commun 402:390–395.  https://doi.org/10.1016/j.bbrc.2010.10.042CrossRefPubMedPubMedCentralGoogle Scholar
  311. Lal A, Navarro F, Maher CA et al (2009) miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to “seedless” 3′UTR microRNA recognition elements. Mol Cell 35:610–625.  https://doi.org/10.1016/j.molcel.2009.08.020CrossRefPubMedPubMedCentralGoogle Scholar
  312. Landau D-A, Slack FJ (2011) MicroRNAs in mutagenesis, genomic instability, and DNA repair. Semin Oncol 38:743–751.  https://doi.org/10.1053/j.seminoncol.2011.08.003CrossRefPubMedPubMedCentralGoogle Scholar
  313. Laplante M, Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149:274–293.  https://doi.org/10.1016/j.cell.2012.03.017CrossRefPubMedPubMedCentralGoogle Scholar
  314. Lassmann T, Maida Y, Tomaru Y et al (2015) Telomerase reverse transcriptase regulates microRNAs. Int J Mol Sci 16:1192–1208.  https://doi.org/10.3390/ijms16011192CrossRefPubMedPubMedCentralGoogle Scholar
  315. Le Floch R, Chiche J, Marchiq I et al (2011) CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors. Proc Natl Acad Sci U S A 108:16663–16668.  https://doi.org/10.1073/pnas.1106123108CrossRefPubMedPubMedCentralGoogle Scholar
  316. Le A, Cooper CR, Gouw AM et al (2010) Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci U S A 107:2037–2042.  https://doi.org/10.1073/pnas.0914433107CrossRefPubMedPubMedCentralGoogle Scholar
  317. Le A, Lane AN, Hamaker M et al (2012) Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab 15:110–121.  https://doi.org/10.1016/j.cmet.2011.12.009CrossRefPubMedPubMedCentralGoogle Scholar
  318. Lee SH, Shin MS, Park WS et al (1999a) Alterations of Fas (Apo-1/CD95) gene in non-small cell lung cancer. Oncogene 18:3754–3760.  https://doi.org/10.1038/sj.onc.1202769CrossRefPubMedPubMedCentralGoogle Scholar
  319. Lee SH, Shin MS, Park WS et al (1999b) Alterations of Fas (APO-1/CD95) gene in transitional cell carcinomas of urinary bladder. Cancer Res 59:3068–3072PubMedPubMedCentralGoogle Scholar
  320. Lee GK, Park HJ, Macleod M et al (2002) Tryptophan deprivation sensitizes activated T cells to apoptosis prior to cell division. Immunology 107:452–460PubMedPubMedCentralCrossRefGoogle Scholar
  321. Lee J-H, Jang H, Lee S-M et al (2015) ATP-citrate lyase regulates cellular senescence via an AMPK- and p53-dependent pathway. FEBS J 282:361–371.  https://doi.org/10.1111/febs.13139CrossRefPubMedPubMedCentralGoogle Scholar
  322. Lei Z, Li B, Yang Z et al (2009) Regulation of HIF-1alpha and VEGF by miR-20b tunes tumor cells to adapt to the alteration of oxygen concentration. PLoS One 4:e7629.  https://doi.org/10.1371/journal.pone.0007629CrossRefPubMedPubMedCentralGoogle Scholar
  323. Ley TJ, Ding L, Walter MJ et al (2010) DNMT3A mutations in acute myeloid leukemia. N Engl J Med 363:2424–2433.  https://doi.org/10.1056/NEJMoa1005143CrossRefPubMedPubMedCentralGoogle Scholar
  324. Li Y, Tergaonkar V (2014) Noncanonical functions of telomerase: implications in telomerase-targeted cancer therapies. Cancer Res 74:1639–1644.  https://doi.org/10.1158/0008-5472.CAN-13-3568CrossRefPubMedPubMedCentralGoogle Scholar
  325. Li Z, Zhang H (2016) Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression. Cell Mol Life Sci 73:377–392.  https://doi.org/10.1007/s00018-015-2070-4CrossRefPubMedPubMedCentralGoogle Scholar
  326. Li ZY, Zou SQ (2001) Fas counterattack in cholangiocarcinoma: a mechanism for immune evasion in human hilar cholangiocarcinomas. World J Gastroenterol 7:860–863PubMedPubMedCentralCrossRefGoogle Scholar
  327. Li X, Chen Y-T, Josson S et al (2013) MicroRNA-185 and 342 inhibit tumorigenicity and induce apoptosis through blockade of the SREBP metabolic pathway in prostate cancer cells. PLoS One 8:e70987.  https://doi.org/10.1371/journal.pone.0070987CrossRefPubMedPubMedCentralGoogle Scholar
  328. Li Y, Han W, Ni T-T et al (2015) Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells. Oncol Rep 33:2821–2828.  https://doi.org/10.3892/or.2015.3884CrossRefPubMedPubMedCentralGoogle Scholar
  329. Li J, Tian H, Yang J, Gong Z (2016a) Long Noncoding RNAs Regulate Cell Growth, Proliferation, and Apoptosis. DNA Cell Biol 35:459–470.  https://doi.org/10.1089/dna.2015.3187CrossRefPubMedPubMedCentralGoogle Scholar
  330. Li Q, Johnston N, Zheng X et al (2016b) miR-28 modulates exhaustive differentiation of T cells through silencing programmed cell death-1 and regulating cytokine secretion. Oncotarget 7:53735–53750.  https://doi.org/10.18632/oncotarget.10731CrossRefPubMedPubMedCentralGoogle Scholar
  331. Liang Y-C, Wu C-H, Chu J-S et al (2005) Involvement of fatty acid-CoA ligase 4 in hepatocellular carcinoma growth: roles of cyclic AMP and p38 mitogen-activated protein kinase. World J Gastroenterol 11:2557–2563PubMedPubMedCentralCrossRefGoogle Scholar
  332. Liang L, Zhu J, Zaorsky NG et al (2014) MicroRNA-223 enhances radiation sensitivity of U87MG cells in vitro and in vivo by targeting ataxia telangiectasia mutated. Int J Radiat Oncol Biol Phys 88:955–960.  https://doi.org/10.1016/j.ijrobp.2013.12.036CrossRefPubMedPubMedCentralGoogle Scholar
  333. Lima RT, Busacca S, Almeida GM et al (2011) MicroRNA regulation of core apoptosis pathways in cancer. Eur J Cancer Oxf Engl 47:163–174.  https://doi.org/10.1016/j.ejca.2010.11.005CrossRefGoogle Scholar
  334. Lin R, Tao R, Gao X et al (2013) Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell 51:506–518.  https://doi.org/10.1016/j.molcel.2013.07.002CrossRefPubMedPubMedCentralGoogle Scholar
  335. Listerman I, Sun J, Gazzaniga FS et al (2013) The major reverse transcriptase-incompetent splice variant of the human telomerase protein inhibits telomerase activity but protects from apoptosis. Cancer Res 73:2817–2828.  https://doi.org/10.1158/0008-5472.CAN-12-3082CrossRefPubMedPubMedCentralGoogle Scholar
  336. Liu Y, Zuckier LS, Ghesani NV (2010) Dominant uptake of fatty acid over glucose by prostate cells: a potential new diagnostic and therapeutic approach. Anticancer Res 30:369–374PubMedPubMedCentralGoogle Scholar
  337. Liu L-Z, Li C, Chen Q et al (2011) MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression. PLoS One 6:e19139.  https://doi.org/10.1371/journal.pone.0019139CrossRefPubMedPubMedCentralGoogle Scholar
  338. Liu P, Xu B, Shen W et al (2012a) Dysregulation of TNFα-induced necroptotic signaling in chronic lymphocytic leukemia: suppression of CYLD gene by LEF1. Leukemia 26:1293–1300.  https://doi.org/10.1038/leu.2011.357CrossRefPubMedPubMedCentralGoogle Scholar
  339. Liu X, Li D, Zhang W et al (2012b) Long non-coding RNA gadd7 interacts with TDP-43 and regulates Cdk6 mRNA decay. EMBO J 31:4415–4427.  https://doi.org/10.1038/emboj.2012.292CrossRefPubMedPubMedCentralGoogle Scholar
  340. Liu Z, Liu J, Segura MF et al (2012c) MiR-182 overexpression in tumourigenesis of high-grade serous ovarian carcinoma. J Pathol 228:204–215.  https://doi.org/10.1002/path.4000CrossRefPubMedPubMedCentralGoogle Scholar
  341. Liu H, Pan Y, Han X et al (2017) MicroRNA-216a promotes the metastasis and epithelial-mesenchymal transition of ovarian cancer by suppressing the PTEN/AKT pathway. OncoTargets Ther 10:2701–2709.  https://doi.org/10.2147/OTT.S114318CrossRefGoogle Scholar
  342. Loeb LA, Loeb KR, Anderson JP (2003) Multiple mutations and cancer. Proc Natl Acad Sci U S A 100:776–781.  https://doi.org/10.1073/pnas.0334858100CrossRefPubMedPubMedCentralGoogle Scholar
  343. López-Ríos F, Sánchez-Aragó M, García-García E et al (2007) Loss of the mitochondrial bioenergetic capacity underlies the glucose avidity of carcinomas. Cancer Res 67:9013–9017.  https://doi.org/10.1158/0008-5472.CAN-07-1678CrossRefPubMedPubMedCentralGoogle Scholar
  344. Low KC, Tergaonkar V (2013) Telomerase: central regulator of all of the hallmarks of cancer. Trends Biochem Sci 38:426–434.  https://doi.org/10.1016/j.tibs.2013.07.001CrossRefPubMedPubMedCentralGoogle Scholar
  345. Lu L, Katsaros D, de la Longrais IAR et al (2007) Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-II expression and favorable prognosis. Cancer Res 67:10117–10122.  https://doi.org/10.1158/0008-5472.CAN-07-2544CrossRefPubMedPubMedCentralGoogle Scholar
  346. Lu W, Pelicano H, Huang P (2010) Cancer metabolism: is glutamine sweeter than glucose? Cancer Cell 18:199–200.  https://doi.org/10.1016/j.ccr.2010.08.017CrossRefPubMedPubMedCentralGoogle Scholar
  347. Luo Z, Feng X, Wang H, Xu W, Zhao Y, Ma W, Jiang S, Liu D, Huang J, Songyang Z (2015) Mir-23a induces telomere dysfunction and cellular senescence by inhibiting TRF2 expression. Aging Cell 14(3):391–399PubMedPubMedCentralCrossRefGoogle Scholar
  348. Luke B, Panza A, Redon S et al (2008) The Rat1p 5′ to 3′ exonuclease degrades telomeric repeat-containing RNA and promotes telomere elongation in Saccharomyces cerevisiae. Mol Cell 32:465–477.  https://doi.org/10.1016/j.molcel.2008.10.019CrossRefPubMedPubMedCentralGoogle Scholar
  349. Lung RW-M, Tong JH-M, To K-F (2013) Emerging roles of small Epstein-Barr virus derived non-coding RNAs in epithelial malignancy. Int J Mol Sci 14:17378–17409.  https://doi.org/10.3390/ijms140917378CrossRefPubMedPubMedCentralGoogle Scholar
  350. Lunt SY, Vander Heiden MG (2011) Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol 27:441–464.  https://doi.org/10.1146/annurev-cellbio-092910-154237CrossRefPubMedPubMedCentralGoogle Scholar
  351. Ma Y, Han W, Yang L et al (2015) The regulation of miRNAs in inflammation-related carcinogenesis. Curr Pharm Des 21:3023–3031PubMedCrossRefPubMedCentralGoogle Scholar
  352. Maas S, Warskulat U, Steinhoff C et al (2004) Decreased Fas expression in advanced-stage bladder cancer is not related to p53 status. Urology 63:392–397.  https://doi.org/10.1016/j.urology.2003.08.023CrossRefPubMedPubMedCentralGoogle Scholar
  353. MacFarlane M, Harper N, Snowden RT et al (2002) Mechanisms of resistance to TRAIL-induced apoptosis in primary B cell chronic lymphocytic leukaemia. Oncogene 21:6809–6818.  https://doi.org/10.1038/sj.onc.1205853CrossRefPubMedGoogle Scholar
  354. Macheda ML, Rogers S, Best JD (2005) Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol 202:654–662.  https://doi.org/10.1002/jcp.20166CrossRefPubMedGoogle Scholar
  355. Madanecki P, Kapoor N, Bebok Z et al (2013) Regulation of angiogenesis by hypoxia: the role of microRNA. Cell Mol Biol Lett 18:47–57.  https://doi.org/10.2478/s11658-012-0037-0CrossRefPubMedGoogle Scholar
  356. Maicher A, Kastner L, Luke B (2012) Telomeres and disease: enter TERRA. RNA Biol 9:843–849.  https://doi.org/10.4161/rna.20330CrossRefPubMedGoogle Scholar
  357. Maida Y, Yasukawa M, Furuuchi M et al (2009) An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA. Nature 461:230–235.  https://doi.org/10.1038/nature08283CrossRefPubMedPubMedCentralGoogle Scholar
  358. Malkin D, Li FP, Strong LC et al (1990) Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250:1233–1238PubMedCrossRefGoogle Scholar
  359. Malumbres M, Barbacid M (2001) To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer 1:222–231.  https://doi.org/10.1038/35106065CrossRefPubMedGoogle Scholar
  360. Mani SR, Juliano CE (2013) Untangling the web: the diverse functions of the PIWI/piRNA pathway. Mol Reprod Dev 80:632–664.  https://doi.org/10.1002/mrd.22195CrossRefPubMedPubMedCentralGoogle Scholar
  361. Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444.  https://doi.org/10.1038/nature07205CrossRefPubMedGoogle Scholar
  362. Mantovani A, Garlanda C, Allavena P (2010) Molecular pathways and targets in cancer-related inflammation. Ann Med 42:161–170.  https://doi.org/10.3109/07853890903405753CrossRefPubMedGoogle Scholar
  363. Martin M, Beauvoit B, Voisin PJ et al (1998) Energetic and morphological plasticity of C6 glioma cells grown on 3-D support; effect of transient glutamine deprivation. J Bioenerg Biomembr 30:565–578PubMedCrossRefGoogle Scholar
  364. Martínez P, Thanasoula M, Muñoz P et al (2009) Increased telomere fragility and fusions resulting from TRF1 deficiency lead to degenerative pathologies and increased cancer in mice. Genes Dev 23:2060–2075.  https://doi.org/10.1101/gad.543509CrossRefPubMedPubMedCentralGoogle Scholar
  365. Maruyama R, Suzuki H, Yamamoto E et al (2012) Emerging links between epigenetic alterations and dysregulation of noncoding RNAs in cancer. Tumour Biol 33:277–285.  https://doi.org/10.1007/s13277-011-0308-9CrossRefPubMedPubMedCentralGoogle Scholar
  366. Masliah-Planchon J, Garinet S, Pasmant E (2016) RAS-MAPK pathway epigenetic activation in cancer: miRNAs in action. Oncotarget 7:38892–38907.  https://doi.org/10.18632/oncotarget.6476CrossRefPubMedPubMedCentralGoogle Scholar
  367. Mason JM, Frydrychova RC, Biessmann H (2008) Drosophila telomeres: an exception providing new insights. BioEssays News Rev Mol Cell Dev Biol 30:25–37.  https://doi.org/10.1002/bies.20688CrossRefGoogle Scholar
  368. Mathupala SP, Ko YH, Pedersen PL (2006) Hexokinase II: cancer’s double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene 25:4777–4786.  https://doi.org/10.1038/sj.onc.1209603CrossRefPubMedPubMedCentralGoogle Scholar
  369. Matouk I, Raveh E, Ohana P et al (2013) The increasing complexity of the oncofetal h19 gene locus: functional dissection and therapeutic intervention. Int J Mol Sci 14:4298–4316.  https://doi.org/10.3390/ijms14024298CrossRefPubMedPubMedCentralGoogle Scholar
  370. Mazurek S, Boschek CB, Hugo F, Eigenbrodt E (2005) Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol 15:300–308.  https://doi.org/10.1016/j.semcancer.2005.04.009CrossRefGoogle Scholar
  371. McCleland ML, Adler AS, Shang Y et al (2012) An integrated genomic screen identifies LDHB as an essential gene for triple-negative breast cancer. Cancer Res 72:5812–5823.  https://doi.org/10.1158/0008-5472.CAN-12-1098CrossRefPubMedPubMedCentralGoogle Scholar
  372. McLaughlin-Drubin ME, Munger K (2008) Viruses Associated with Human Cancer. Biochim Biophys Acta 1782:127–150.  https://doi.org/10.1016/j.bbadis.2007.12.005CrossRefPubMedPubMedCentralGoogle Scholar
  373. Medema JP, de Jong J, Peltenburg LT et al (2001) Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors. Proc Natl Acad Sci U S A 98:11515–11520.  https://doi.org/10.1073/pnas.201398198CrossRefPubMedPubMedCentralGoogle Scholar
  374. Meena J, Rudolph KL, Günes C (2015) Telomere dysfunction, chromosomal instability and cancer. Recent Results Cancer Res 200:61–79.  https://doi.org/10.1007/978-3-319-20291-4_3CrossRefPubMedPubMedCentralGoogle Scholar
  375. Mehrotra A, Joshi K, Kaul D (2010) E2F-1 RNomics is critical for reprogramming of cancer cells to quiescent state. Int J Cancer 127:849–858.  https://doi.org/10.1002/ijc.25109CrossRefPubMedGoogle Scholar
  376. Menendez JA, Lupu R (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 7:763–777.  https://doi.org/10.1038/nrc2222CrossRefPubMedGoogle Scholar
  377. Meng F, Henson R, Wehbe-Janek H et al (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133:647–658.  https://doi.org/10.1053/j.gastro.2007.05.022CrossRefPubMedPubMedCentralGoogle Scholar
  378. Meng M-B, Wang H-H, Cui Y-L et al (2016) Necroptosis in tumorigenesis, activation of anti-tumor immunity, and cancer therapy. Oncotarget 7:57391–57413.  https://doi.org/10.18632/oncotarget.10548CrossRefPubMedPubMedCentralGoogle Scholar
  379. Mesri EA, Feitelson MA, Munger K (2014) Human viral oncogenesis: a cancer hallmarks analysis. Cell Host Microbe 15:266–282.  https://doi.org/10.1016/j.chom.2014.02.011CrossRefPubMedPubMedCentralGoogle Scholar
  380. Metallo CM, Gameiro PA, Bell EL et al (2011) Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 481:380–384.  https://doi.org/10.1038/nature10602CrossRefPubMedPubMedCentralGoogle Scholar
  381. Minchenko O, Opentanova I, Caro J (2003) Hypoxic regulation of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene family (PFKFB-1-4) expression in vivo. FEBS Lett 554:264–270PubMedCrossRefGoogle Scholar
  382. Minchenko OH, Ochiai A, Opentanova IL et al (2005) Overexpression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4 in the human breast and colon malignant tumors. Biochimie 87:1005–1010.  https://doi.org/10.1016/j.biochi.2005.04.007CrossRefPubMedGoogle Scholar
  383. Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191:144–148PubMedCrossRefGoogle Scholar
  384. Mladenov E, Magin S, Soni A, Iliakis G (2016) DNA double-strand-break repair in higher eukaryotes and its role in genomic instability and cancer: Cell cycle and proliferation-dependent regulation. Semin Cancer Biol 37–38:51–64.  https://doi.org/10.1016/j.semcancer.2016.03.003CrossRefPubMedGoogle Scholar
  385. Moore PS, Chang Y (2010) Why do viruses cause cancer? Highlights of the first century of human tumour virology. Nat Rev Cancer 10:878–889.  https://doi.org/10.1038/nrc2961CrossRefPubMedPubMedCentralGoogle Scholar
  386. Morales-Sánchez A, Fuentes-Pananá EM (2014) Human viruses and cancer. Viruses 6:4047–4079.  https://doi.org/10.3390/v6104047CrossRefPubMedPubMedCentralGoogle Scholar
  387. Morgan DO (1995) Principles of CDK regulation. Nature 374:131–134.  https://doi.org/10.1038/374131a0CrossRefPubMedGoogle Scholar
  388. Moskwa P, Buffa FM, Pan Y et al (2011) miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors. Mol Cell 41:210–220.  https://doi.org/10.1016/j.molcel.2010.12.005CrossRefPubMedGoogle Scholar
  389. Moussaieff A, Rouleau M, Kitsberg D et al (2015) Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells. Cell Metab 21:392–402.  https://doi.org/10.1016/j.cmet.2015.02.002CrossRefPubMedGoogle Scholar
  390. Moyano M, Stefani G (2015) piRNA involvement in genome stability and human cancer. J Hematol Oncol 8:38.  https://doi.org/10.1186/s13045-015-0133-5CrossRefPubMedPubMedCentralGoogle Scholar
  391. Mukherjee S, Firpo EJ, Wang Y, Roberts JM (2011) Separation of telomerase functions by reverse genetics. Proc Natl Acad Sci U S A 108:E1363–E1371.  https://doi.org/10.1073/pnas.1112414108CrossRefPubMedPubMedCentralGoogle Scholar
  392. Nagy JA, Chang S-H, Shih S-C et al (2010) Heterogeneity of the tumor vasculature. Semin Thromb Hemost 36:321–331.  https://doi.org/10.1055/s-0030-1253454CrossRefPubMedPubMedCentralGoogle Scholar
  393. Napier CE, Huschtscha LI, Harvey A et al (2015) ATRX represses alternative lengthening of telomeres. Oncotarget 6:16543–16558.  https://doi.org/10.18632/oncotarget.3846CrossRefPubMedPubMedCentralGoogle Scholar
  394. Nergadze SG, Farnung BO, Wischnewski H et al (2009) CpG-island promoters drive transcription of human telomeres. RNA 15:2186–2194.  https://doi.org/10.1261/rna.1748309CrossRefPubMedPubMedCentralGoogle Scholar
  395. Newman MA, Thomson JM, Hammond SM (2008) Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing. RNA 14:1539–1549.  https://doi.org/10.1261/rna.1155108CrossRefPubMedPubMedCentralGoogle Scholar
  396. Newsholme EA, Crabtree B, Ardawi MS (1985) The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells. Biosci Rep 5:393–400PubMedCrossRefGoogle Scholar
  397. Ng LJ, Cropley JE, Pickett HA et al (2009) Telomerase activity is associated with an increase in DNA methylation at the proximal subtelomere and a reduction in telomeric transcription. Nucleic Acids Res 37:1152–1159.  https://doi.org/10.1093/nar/gkn1030CrossRefPubMedPubMedCentralGoogle Scholar
  398. Ng WL, Yan D, Zhang X et al (2010) Over-expression of miR-100 is responsible for the low-expression of ATM in the human glioma cell line: M059J. DNA Repair 9:1170–1175.  https://doi.org/10.1016/j.dnarep.2010.08.007CrossRefPubMedPubMedCentralGoogle Scholar
  399. Nicholls DG, Rial E (1999) A history of the first uncoupling protein, UCP1. J Bioenerg Biomembr 31:399–406PubMedCrossRefGoogle Scholar
  400. Nicklin P, Bergman P, Zhang B et al (2009) Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 136:521–534.  https://doi.org/10.1016/j.cell.2008.11.044CrossRefPubMedPubMedCentralGoogle Scholar
  401. Nikitin PA, Luftig MA (2012) The DNA damage response in viral-induced cellular transformation. Br J Cancer 106:429–435.  https://doi.org/10.1038/bjc.2011.612CrossRefPubMedPubMedCentralGoogle Scholar
  402. Nishimura J, Handa R, Yamamoto H et al (2012) microRNA-181a is associated with poor prognosis of colorectal cancer. Oncol Rep 28:2221–2226.  https://doi.org/10.3892/or.2012.2059CrossRefPubMedPubMedCentralGoogle Scholar
  403. Nowak T, Januszkiewicz D, Zawada M et al (2006) Amplification of hTERT and hTERC genes in leukemic cells with high expression and activity of telomerase. Oncol Rep 16:301–305PubMedPubMedCentralGoogle Scholar
  404. Nurse P (2002) Cyclin dependent kinases and cell cycle control (nobel lecture). Chembiochem Eur J Chem Biol 3:596–603.  https://doi.org/10.1002/1439-7633(20020703)3:7<596::AID-CBIC596>3.0.CO;2-UCrossRefGoogle Scholar
  405. O’Donnell KA, Wentzel EA, Zeller KI et al (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435:839–843.  https://doi.org/10.1038/nature03677CrossRefPubMedPubMedCentralGoogle Scholar
  406. O’Sullivan RJ, Almouzni G (2014) Assembly of telomeric chromatin to create ALTernative endings. Trends Cell Biol 24:675–685.  https://doi.org/10.1016/j.tcb.2014.07.007CrossRefPubMedPubMedCentralGoogle Scholar
  407. O’Sullivan RJ, Karlseder J (2010) Telomeres: protecting chromosomes against genome instability. Nat Rev Mol Cell Biol 11:171–181.  https://doi.org/10.1038/nrm2848CrossRefPubMedPubMedCentralGoogle Scholar
  408. Ohm JE, Gabrilovich DI, Sempowski GD et al (2003) VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression. Blood 101:4878–4886.  https://doi.org/10.1182/blood-2002-07-1956CrossRefPubMedPubMedCentralGoogle Scholar
  409. Ohta A, Gorelik E, Prasad SJ et al (2006) A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci U S A 103:13132–13137.  https://doi.org/10.1073/pnas.0605251103CrossRefPubMedPubMedCentralGoogle Scholar
  410. Okamoto N, Yasukawa M, Nguyen C et al (2011) Maintenance of tumor initiating cells of defined genetic composition by nucleostemin. Proc Natl Acad Sci U S A 108:20388–20393.  https://doi.org/10.1073/pnas.1015171108CrossRefPubMedPubMedCentralGoogle Scholar
  411. Okamura K, Lai EC (2008) Endogenous small interfering RNAs in animals. Nat Rev Mol Cell Biol 9:673–678.  https://doi.org/10.1038/nrm2479CrossRefPubMedPubMedCentralGoogle Scholar
  412. Olive V, Bennett MJ, Walker JC et al (2009) miR-19 is a key oncogenic component of mir-17-92. Genes Dev 23:2839–2849.  https://doi.org/10.1101/gad.1861409CrossRefPubMedPubMedCentralGoogle Scholar
  413. Olsson A-K, Dimberg A, Kreuger J, Claesson-Welsh L (2006) VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol 7:359–371.  https://doi.org/10.1038/nrm1911CrossRefPubMedPubMedCentralGoogle Scholar
  414. Ozkaya AB, Ak H, Atay S, Aydin HH (2015) Targeting mitochondrial citrate transport in breast cancer cell lines. Anti Cancer Agents Med Chem 15:374–381CrossRefGoogle Scholar
  415. Pagès F, Galon J, Dieu-Nosjean M-C et al (2010) Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene 29:1093–1102.  https://doi.org/10.1038/onc.2009.416CrossRefPubMedPubMedCentralGoogle Scholar
  416. Palm W, de Lange T (2008) How shelterin protects mammalian telomeres. Annu Rev Genet 42:301–334.  https://doi.org/10.1146/annurev.genet.41.110306.130350CrossRefGoogle Scholar
  417. Pan Y, Mansfield KD, Bertozzi CC et al (2007) Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Mol Cell Biol 27:912–925.  https://doi.org/10.1128/MCB.01223-06CrossRefPubMedPubMedCentralGoogle Scholar
  418. Pandya D, Mariani M, He S et al (2015) Epstein-barr virus MicroRNA expression increases aggressiveness of solid malignancies. PLoS One 10:e0136058.  https://doi.org/10.1371/journal.pone.0136058CrossRefPubMedPubMedCentralGoogle Scholar
  419. Paoli P, Giannoni E, Chiarugi P (2013) Anoikis molecular pathways and its role in cancer progression. Biochim Biophys Acta 1833:3481–3498.  https://doi.org/10.1016/j.bbamcr.2013.06.026CrossRefPubMedPubMedCentralGoogle Scholar
  420. Papandreou I, Lim AL, Laderoute K, Denko NC (2008) Hypoxia signals autophagy in tumor cells via AMPK activity, independent of HIF-1, BNIP3, and BNIP3L. Cell Death Differ 15:1572–1581.  https://doi.org/10.1038/cdd.2008.84CrossRefPubMedPubMedCentralGoogle Scholar
  421. Park J-I, Venteicher AS, Hong JY et al (2009) Telomerase modulates Wnt signalling by association with target gene chromatin. Nature 460:66–72.  https://doi.org/10.1038/nature08137CrossRefPubMedPubMedCentralGoogle Scholar
  422. Pasmant E, Laurendeau I, Héron D et al (2007) Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF. Cancer Res 67:3963–3969.  https://doi.org/10.1158/0008-5472.CAN-06-2004CrossRefPubMedPubMedCentralGoogle Scholar
  423. Paumen MB, Ishida Y, Han H et al (1997) Direct interaction of the mitochondrial membrane protein carnitine palmitoyltransferase I with Bcl-2. Biochem Biophys Res Commun 231:523–525.  https://doi.org/10.1006/bbrc.1997.6089CrossRefPubMedPubMedCentralGoogle Scholar
  424. Pavlides S, Whitaker-Menezes D, Castello-Cros R et al (2009) The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle Georget Tex 8:3984–4001.  https://doi.org/10.4161/cc.8.23.10238CrossRefGoogle Scholar
  425. Pavlova NN, Thompson CB (2016) The emerging hallmarks of cancer metabolism. Cell Metab 23:27–47.  https://doi.org/10.1016/j.cmet.2015.12.006CrossRefPubMedPubMedCentralGoogle Scholar
  426. Pedram M, Sprung CN, Gao Q et al (2006) Telomere position effect and silencing of transgenes near telomeres in the mouse. Mol Cell Biol 26:1865–1878.  https://doi.org/10.1128/MCB.26.5.1865-1878.2006CrossRefPubMedPubMedCentralGoogle Scholar
  427. Penke TJR, McKay DJ, Strahl BD et al (2016) Direct interrogation of the role of H3K9 in metazoan heterochromatin function. Genes Dev 30:1866–1880.  https://doi.org/10.1101/gad.286278.116CrossRefPubMedPubMedCentralGoogle Scholar
  428. Pitti RM, Marsters SA, Lawrence DA et al (1998) Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature 396:699–703.  https://doi.org/10.1038/25387CrossRefPubMedPubMedCentralGoogle Scholar
  429. Plescia OJ, Smith AH, Grinwich K (1975) Subversion of immune system by tumor cells and role of prostaglandins. Proc Natl Acad Sci U S A 72:1848–1851PubMedPubMedCentralCrossRefGoogle Scholar
  430. Poiesz BJ, Ruscetti FW, Gazdar AF et al (1980) Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A 77:7415–7419PubMedPubMedCentralCrossRefGoogle Scholar
  431. Polet F, Feron O (2013) Endothelial cell metabolism and tumour angiogenesis: glucose and glutamine as essential fuels and lactate as the driving force. J Intern Med 273:156–165.  https://doi.org/10.1111/joim.12016CrossRefPubMedPubMedCentralGoogle Scholar
  432. Porro A, Feuerhahn S, Reichenbach P, Lingner J (2010) Molecular dissection of telomeric repeat-containing RNA biogenesis unveils the presence of distinct and multiple regulatory pathways. Mol Cell Biol 30:4808–4817.  https://doi.org/10.1128/MCB.00460-10CrossRefPubMedPubMedCentralGoogle Scholar
  433. Porro A, Feuerhahn S, Delafontaine J et al (2014a) Functional characterization of the TERRA transcriptome at damaged telomeres. Nat Commun 5:5379.  https://doi.org/10.1038/ncomms6379CrossRefPubMedPubMedCentralGoogle Scholar
  434. Porro A, Feuerhahn S, Lingner J (2014b) TERRA-reinforced association of LSD1 with MRE11 promotes processing of uncapped telomeres. Cell Rep 6:765–776.  https://doi.org/10.1016/j.celrep.2014.01.022CrossRefPubMedPubMedCentralGoogle Scholar
  435. Porta C, Larghi P, Rimoldi M et al (2009) Cellular and molecular pathways linking inflammation and cancer. Immunobiology 214:761–777.  https://doi.org/10.1016/j.imbio.2009.06.014CrossRefPubMedPubMedCentralGoogle Scholar
  436. Postepska-Igielska A, Krunic D, Schmitt N et al (2013) The chromatin remodelling complex NoRC safeguards genome stability by heterochromatin formation at telomeres and centromeres. EMBO Rep 14:704–710.  https://doi.org/10.1038/embor.2013.87CrossRefPubMedPubMedCentralGoogle Scholar
  437. Puig-Kröger A, Pello OM, Muñiz-Pello O et al (2003) Peritoneal dialysis solutions inhibit the differentiation and maturation of human monocyte-derived dendritic cells: effect of lactate and glucose-degradation products. J Leukoc Biol 73:482–492PubMedCrossRefPubMedCentralGoogle Scholar
  438. Qi J, Yu J-Y, Shcherbata HR et al (2009) microRNAs regulate human embryonic stem cell division. Cell Cycle Georget Tex 8:3729–3741CrossRefGoogle Scholar
  439. Qin J, Li W, Gao S-J, Lu C (2017) KSHV microRNAs: tricks of the Devil. Trends Microbiol.  https://doi.org/10.1016/j.tim.2017.02.002PubMedCrossRefPubMedCentralGoogle Scholar
  440. Qiu B, Ackerman D, Sanchez DJ et al (2015) HIF2α-dependent lipid storage promotes endoplasmic reticulum homeostasis in clear-cell renal cell carcinoma. Cancer Discov 5:652–667.  https://doi.org/10.1158/2159-8290.CD-14-1507CrossRefPubMedPubMedCentralGoogle Scholar
  441. Radogna F, Dicato M, Diederich M (2015) Cancer-type-specific crosstalk between autophagy, necroptosis and apoptosis as a pharmacological target. Biochem Pharmacol 94:1–11.  https://doi.org/10.1016/j.bcp.2014.12.018CrossRefPubMedPubMedCentralGoogle Scholar
  442. Raica M, Cimpean AM, Ribatti D (2009) Angiogenesis in pre-malignant conditions. Eur J Cancer Oxf Engl 45:1924–1934.  https://doi.org/10.1016/j.ejca.2009.04.007CrossRefGoogle Scholar
  443. Ramana CV, Boldogh I, Izumi T, Mitra S (1998) Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals. Proc Natl Acad Sci U S A 95:5061–5066PubMedPubMedCentralCrossRefGoogle Scholar
  444. Ramsay AJ, Quesada V, Foronda M et al (2013) POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia. Nat Genet 45:526–530.  https://doi.org/10.1038/ng.2584CrossRefPubMedPubMedCentralGoogle Scholar
  445. Raynor A, Jantscheff P, Ross T et al (2015) Saturated and mono-unsaturated lysophosphatidylcholine metabolism in tumour cells: a potential therapeutic target for preventing metastases. Lipids Health Dis 14:69.  https://doi.org/10.1186/s12944-015-0070-xCrossRefPubMedPubMedCentralGoogle Scholar
  446. Rebollo R, Romanish MT, Mager DL (2012) Transposable elements: an abundant and natural source of regulatory sequences for host genes. Annu Rev Genet 46:21–42.  https://doi.org/10.1146/annurev-genet-110711-155621CrossRefPubMedPubMedCentralGoogle Scholar
  447. Redon S, Reichenbach P, Lingner J (2010) The non-coding RNA TERRA is a natural ligand and direct inhibitor of human telomerase. Nucleic Acids Res 38:5797–5806.  https://doi.org/10.1093/nar/gkq296CrossRefPubMedPubMedCentralGoogle Scholar
  448. Regad T (2015) Targeting RTK signaling pathways in cancer. Cancer 7:1758–1784.  https://doi.org/10.3390/cancers7030860CrossRefGoogle Scholar
  449. Reitzer LJ, Wice BM, Kennell D (1979) Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. J Biol Chem 254:2669–2676PubMedPubMedCentralGoogle Scholar
  450. Ren B, Yee KO, Lawler J, Khosravi-Far R (2006) Regulation of tumor angiogenesis by thrombospondin-1. Biochim Biophys Acta 1765:178–188.  https://doi.org/10.1016/j.bbcan.2005.11.002CrossRefPubMedPubMedCentralGoogle Scholar
  451. Renehan AG, Frystyk J, Flyvbjerg A (2006) Obesity and cancer risk: the role of the insulin-IGF axis. Trends Endocrinol Metab 17:328–336.  https://doi.org/10.1016/j.tem.2006.08.006CrossRefPubMedPubMedCentralGoogle Scholar
  452. Rhee I, Bachman KE, Park BH et al (2002) DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature 416:552–556.  https://doi.org/10.1038/416552aCrossRefPubMedPubMedCentralGoogle Scholar
  453. Rhind N, Russell P (2012) Signaling pathways that regulate cell division. Cold Spring Harb Perspect Biol.  https://doi.org/10.1101/cshperspect.a005942PubMedPubMedCentralCrossRefGoogle Scholar
  454. Ribatti D (2009) Endogenous inhibitors of angiogenesis: a historical review. Leuk Res 33:638–644.  https://doi.org/10.1016/j.leukres.2008.11.019CrossRefPubMedPubMedCentralGoogle Scholar
  455. Rigal M, Mathieu O (2011) A “mille-feuille” of silencing: epigenetic control of transposable elements. Biochim Biophys Acta 1809:452–458.  https://doi.org/10.1016/j.bbagrm.2011.04.001CrossRefPubMedPubMedCentralGoogle Scholar
  456. Rinn JL, Huarte M (2011) To repress or not to repress: this is the guardian’s question. Trends Cell Biol 21:344–353.  https://doi.org/10.1016/j.tcb.2011.04.002CrossRefPubMedPubMedCentralGoogle Scholar
  457. Robey RB, Hay N (2006) Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene 25:4683–4696.  https://doi.org/10.1038/sj.onc.1209595CrossRefPubMedPubMedCentralGoogle Scholar
  458. Robey RB, Hay N (2009) Is Akt the “Warburg kinase”?-Akt-energy metabolism interactions and oncogenesis. Semin Cancer Biol 19:25–31.  https://doi.org/10.1016/j.semcancer.2008.11.010CrossRefPubMedPubMedCentralGoogle Scholar
  459. Robin JD, Ludlow AT, Batten K et al (2014) Telomere position effect: regulation of gene expression with progressive telomere shortening over long distances. Genes Dev 28:2464–2476.  https://doi.org/10.1101/gad.251041.114CrossRefPubMedPubMedCentralGoogle Scholar
  460. Rodier F, Coppé J-P, Patil CK et al (2009) Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol 11:973–979.  https://doi.org/10.1038/ncb1909CrossRefPubMedPubMedCentralGoogle Scholar
  461. Rodríguez-Paredes M, Esteller M (2011) Cancer epigenetics reaches mainstream oncology. Nat Med 17:330–339.  https://doi.org/10.1038/nm.2305CrossRefGoogle Scholar
  462. Rotem-Yehudar R, Groettrup M, Soza A et al (1996) LMP-associated proteolytic activities and TAP-dependent peptide transport for class 1 MHC molecules are suppressed in cell lines transformed by the highly oncogenic adenovirus 12. J Exp Med 183:499–514PubMedCrossRefPubMedCentralGoogle Scholar
  463. Roth W, Isenmann S, Nakamura M et al (2001) Soluble decoy receptor 3 is expressed by malignant gliomas and suppresses CD95 ligand-induced apoptosis and chemotaxis. Cancer Res 61:2759–2765PubMedPubMedCentralGoogle Scholar
  464. Rouas-Freiss N, Moreau P, Menier C, Carosella ED (2003) HLA-G in cancer: a way to turn off the immune system. Semin Cancer Biol 13:325–336PubMedCrossRefPubMedCentralGoogle Scholar
  465. Rous P (1911) A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J Exp Med 13:397–411PubMedPubMedCentralCrossRefGoogle Scholar
  466. Rusché LN, Kirchmaier AL, Rine J (2002) Ordered nucleation and spreading of silenced chromatin in Saccharomyces cerevisiae. Mol Biol Cell 13:2207–2222.  https://doi.org/10.1091/mbc.E02-03-0175CrossRefPubMedPubMedCentralGoogle Scholar
  467. Saito K, Siomi MC (2010) Small RNA-mediated quiescence of transposable elements in animals. Dev Cell 19:687–697.  https://doi.org/10.1016/j.devcel.2010.10.011CrossRefPubMedPubMedCentralGoogle Scholar
  468. Sampl S, Pramhas S, Stern C et al (2012) Expression of telomeres in astrocytoma WHO grade 2 to 4: TERRA level correlates with telomere length, telomerase activity, and advanced clinical grade. Transl Oncol 5:56–65PubMedPubMedCentralCrossRefGoogle Scholar
  469. Sampson VB, Rong NH, Han J et al (2007) MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res 67:9762–9770.  https://doi.org/10.1158/0008-5472.CAN-07-2462CrossRefPubMedPubMedCentralGoogle Scholar
  470. Santos CR, Schulze A (2012) Lipid metabolism in cancer. FEBS J 279:2610–2623.  https://doi.org/10.1111/j.1742-4658.2012.08644.xCrossRefPubMedPubMedCentralGoogle Scholar
  471. Santos JH, Meyer JN, Skorvaga M et al (2004) Mitochondrial hTERT exacerbates free-radical-mediated mtDNA damage. Aging Cell 3:399–411.  https://doi.org/10.1111/j.1474-9728.2004.00124.xCrossRefPubMedPubMedCentralGoogle Scholar
  472. Santos JH, Meyer JN, Van Houten B (2006) Mitochondrial localization of telomerase as a determinant for hydrogen peroxide-induced mitochondrial DNA damage and apoptosis. Hum Mol Genet 15:1757–1768.  https://doi.org/10.1093/hmg/ddl098CrossRefPubMedPubMedCentralGoogle Scholar
  473. Sarthy J, Bae NS, Scrafford J, Baumann P (2009) Human RAP1 inhibits non-homologous end joining at telomeres. EMBO J 28:3390–3399.  https://doi.org/10.1038/emboj.2009.275CrossRefPubMedPubMedCentralGoogle Scholar
  474. Schell JC, Olson KA, Jiang L et al (2014) A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and colon cancer cell growth. Mol Cell 56:400–413.  https://doi.org/10.1016/j.molcel.2014.09.026CrossRefPubMedPubMedCentralGoogle Scholar
  475. Schoeftner S, Blasco MA (2008) Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol 10:228–236.  https://doi.org/10.1038/ncb1685CrossRefPubMedGoogle Scholar
  476. Schofield CJ, Ratcliffe PJ (2004) Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 5:343–354.  https://doi.org/10.1038/nrm1366CrossRefPubMedGoogle Scholar
  477. Schultz J, Lorenz P, Gross G et al (2008) MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth. Cell Res 18:549–557.  https://doi.org/10.1038/cr.2008.45CrossRefPubMedGoogle Scholar
  478. Schwitalla S, Fingerle AA, Cammareri P et al (2013) Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell 152:25–38.  https://doi.org/10.1016/j.cell.2012.12.012CrossRefPubMedGoogle Scholar
  479. Sejima T, Isoyama T, Miyagawa I (2003) Alteration of apoptotic regulatory molecules expression during carcinogenesis and tumor progression of renal cell carcinoma. Int J Urol Off J Jpn Urol Assoc 10:476–484Google Scholar
  480. Semenza GL (2000) HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J Appl Physiol 88:1474–1480PubMedCrossRefGoogle Scholar
  481. Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3:721–732.  https://doi.org/10.1038/nrc1187CrossRefPubMedGoogle Scholar
  482. Semenza GL (2008) Tumor metabolism: cancer cells give and take lactate. J Clin Invest 118:3835–3837.  https://doi.org/10.1172/JCI37373CrossRefPubMedPubMedCentralGoogle Scholar
  483. Semenza GL (2010) Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene 29:625–634.  https://doi.org/10.1038/onc.2009.441CrossRefPubMedGoogle Scholar
  484. Senyilmaz D, Teleman AA (2015) Chicken or the egg: Warburg effect and mitochondrial dysfunction. F1000prime Rep 7:41.  https://doi.org/10.12703/P7-41CrossRefPubMedPubMedCentralGoogle Scholar
  485. Shah MA, Denton EL, Arrowsmith CH et al (2014) A global assessment of cancer genomic alterations in epigenetic mechanisms. Epigenetics Chromatin 7:29.  https://doi.org/10.1186/1756-8935-7-29CrossRefPubMedPubMedCentralGoogle Scholar
  486. Shalgi R, Pilpel Y, Oren M (2010) Repression of transposable-elements – a microRNA anti-cancer defense mechanism? Trends Genet TIG 26:253–259.  https://doi.org/10.1016/j.tig.2010.03.006CrossRefPubMedPubMedCentralGoogle Scholar
  487. Shamma A, Takegami Y, Miki T et al (2009) Rb Regulates DNA damage response and cellular senescence through E2F-dependent suppression of N-ras isoprenylation. Cancer Cell 15:255–269.  https://doi.org/10.1016/j.ccr.2009.03.001CrossRefPubMedPubMedCentralGoogle Scholar
  488. Sharma V, Misteli T (2013) Non-coding RNAs in DNA damage and repair. FEBS Lett 587:1832–1839.  https://doi.org/10.1016/j.febslet.2013.05.006CrossRefPubMedPubMedCentralGoogle Scholar
  489. Sharma M, Sharma S, Arora M, Kaul D (2013) Regulation of cellular Cyclin D1 gene by arsenic is mediated through miR-2909. Gene 522:60–64.  https://doi.org/10.1016/j.gene.2013.03.058CrossRefPubMedPubMedCentralGoogle Scholar
  490. Sharma S, Kaul D, Arora M, Malik D (2015) Oncogenic nature of a novel mutant AATF and its interactome existing within human cancer cells. Cell Biol Int 39:326–333.  https://doi.org/10.1002/cbin.10379CrossRefPubMedPubMedCentralGoogle Scholar
  491. Shen G, Li X, Jia Y et al (2013) Hypoxia-regulated microRNAs in human cancer. Acta Pharmacol Sin 34:336–341.  https://doi.org/10.1038/aps.2012.195CrossRefPubMedPubMedCentralGoogle Scholar
  492. Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13:1501–1512PubMedCrossRefPubMedCentralGoogle Scholar
  493. Sherr CJ, Roberts JM (2004) Living with or without cyclins and cyclin-dependent kinases. Genes Dev 18:2699–2711.  https://doi.org/10.1101/gad.1256504CrossRefPubMedPubMedCentralGoogle Scholar
  494. Shi L, Zhang S, Wu H et al (2013) MiR-200c increases the radiosensitivity of non-small-cell lung cancer cell line A549 by targeting VEGF-VEGFR2 pathway. PLoS One 8:e78344.  https://doi.org/10.1371/journal.pone.0078344CrossRefPubMedPubMedCentralGoogle Scholar
  495. Shi J, Yang XR, Ballew B et al (2014) Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma. Nat Genet 46:482–486.  https://doi.org/10.1038/ng.2941CrossRefPubMedPubMedCentralGoogle Scholar
  496. Shim H, Dolde C, Lewis BC et al (1997) c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc Natl Acad Sci U S A 94:6658–6663PubMedPubMedCentralCrossRefGoogle Scholar
  497. Shime H, Yabu M, Akazawa T et al (2008) Tumor-secreted lactic acid promotes IL-23/IL-17 proinflammatory pathway. J Immunol 1950(180):7175–7183CrossRefGoogle Scholar
  498. Shimizu T, Marusawa H, Endo Y, Chiba T (2012) Inflammation-mediated genomic instability: roles of activation-induced cytidine deaminase in carcinogenesis. Cancer Sci 103:1201–1206.  https://doi.org/10.1111/j.1349-7006.2012.02293.xCrossRefGoogle Scholar
  499. Shin MS, Park WS, Kim SY et al (1999) Alterations of Fas (Apo-1/CD95) gene in cutaneous malignant melanoma. Am J Pathol 154:1785–1791.  https://doi.org/10.1016/S0002-9440(10)65434-XCrossRefPubMedPubMedCentralGoogle Scholar
  500. Shulzhenko N, Lyng H, Sanson GF, Morgun A (2014) Ménage à trois: an evolutionary interplay between human papillomavirus, a tumor, and a woman. Trends Microbiol 22:345–353.  https://doi.org/10.1016/j.tim.2014.02.009CrossRefPubMedGoogle Scholar
  501. Singer K, Gottfried E, Kreutz M, Mackensen A (2011) Suppression of T-cell responses by tumor metabolites. Cancer Immunol Immunother 60:425–431.  https://doi.org/10.1007/s00262-010-0967-1CrossRefPubMedGoogle Scholar
  502. Singhapol C, Pal D, Czapiewski R et al (2013) Mitochondrial telomerase protects cancer cells from nuclear DNA damage and apoptosis. PLoS One 8:e52989.  https://doi.org/10.1371/journal.pone.0052989CrossRefPubMedPubMedCentralGoogle Scholar
  503. Slotkin RK, Martienssen R (2007) Transposable elements and the epigenetic regulation of the genome. Nat Rev Genet 8:272–285.  https://doi.org/10.1038/nrg2072CrossRefPubMedPubMedCentralGoogle Scholar
  504. Smith LL, Coller HA, Roberts JM (2003) Telomerase modulates expression of growth-controlling genes and enhances cell proliferation. Nat Cell Biol 5:474–479.  https://doi.org/10.1038/ncb985CrossRefPubMedPubMedCentralGoogle Scholar
  505. Smolle MA, Calin HN, Pichler M, Calin GA (2017) Noncoding RNAs and immune checkpoints-clinical implications as cancer therapeutics. FEBS J.  https://doi.org/10.1111/febs.14030PubMedCrossRefPubMedCentralGoogle Scholar
  506. Song E, Chen J, Ouyang N et al (2001) Soluble Fas ligand released by colon adenocarcinoma cells induces host lymphocyte apoptosis: an active mode of immune evasion in colon cancer. Br J Cancer 85:1047–1054.  https://doi.org/10.1038/sj.bjc.6692042CrossRefPubMedPubMedCentralGoogle Scholar
  507. Sonveaux P, Végran F, Schroeder T et al (2008) Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest 118:3930–3942.  https://doi.org/10.1172/JCI36843CrossRefPubMedPubMedCentralGoogle Scholar
  508. Staveley-O’Carroll K, Sotomayor E, Montgomery J et al (1998) Induction of antigen-specific T cell anergy: An early event in the course of tumor progression. Proc Natl Acad Sci U S A 95:1178–1183PubMedPubMedCentralCrossRefGoogle Scholar
  509. Stehelin D, Varmus HE, Bishop JM, Vogt PK (1976) DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260:170–173PubMedCrossRefPubMedCentralGoogle Scholar
  510. Stewart SE, Eddy BE, Borgese N (1958) Neoplasms in mice inoculated with a tumor agent carried in tissue culture. J Natl Cancer Inst 20:1223–1243PubMedCrossRefPubMedCentralGoogle Scholar
  511. Su Z, Yang Z, Xu Y et al (2015) MicroRNAs in apoptosis, autophagy and necroptosis. Oncotarget 6:8474–8490.  https://doi.org/10.18632/oncotarget.3523CrossRefPubMedPubMedCentralGoogle Scholar
  512. Subramanian M, Jones MF, Lal A (2013) Long non-coding RNAs embedded in the Rb and p53 Pathways. Cancer 5:1655–1675.  https://doi.org/10.3390/cancers5041655CrossRefGoogle Scholar
  513. Sugden MC, Holness MJ (2003) Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs. Am J Physiol Endocrinol Metab 284:E855–E862.  https://doi.org/10.1152/ajpendo.00526.2002CrossRefPubMedPubMedCentralGoogle Scholar
  514. Sussman I, Erecińska M, Wilson DF (1980) Regulation of cellular energy metabolism: the Crabtree effect. Biochim Biophys Acta 591:209–223PubMedCrossRefPubMedCentralGoogle Scholar
  515. Suzuki MM, Bird A (2008) DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9:465–476.  https://doi.org/10.1038/nrg2341CrossRefPubMedPubMedCentralGoogle Scholar
  516. Suzuki M, Yamada T, Kihara-Negishi F et al (2006) Site-specific DNA methylation by a complex of PU.1 and Dnmt3a/b. Oncogene 25:2477–2488.  https://doi.org/10.1038/sj.onc.1209272CrossRefPubMedPubMedCentralGoogle Scholar
  517. Swets M, Zaalberg A, Boot A et al (2016) Tumor LINE-1 Methylation level in association with survival of patients with stage II colon cancer. Int J Mol Sci.  https://doi.org/10.3390/ijms18010036PubMedCentralCrossRefGoogle Scholar
  518. Swinnen JV, Vanderhoydonc F, Elgamal AA et al (2000) Selective activation of the fatty acid synthesis pathway in human prostate cancer. Int J Cancer 88:176–179PubMedCrossRefPubMedCentralGoogle Scholar
  519. Szablewski L (2013) Expression of glucose transporters in cancers. Biochim Biophys Acta 1835:164–169.  https://doi.org/10.1016/j.bbcan.2012.12.004CrossRefPubMedPubMedCentralGoogle Scholar
  520. Szutowicz A, Kwiatkowski J, Angielski S (1979) Lipogenetic and glycolytic enzyme activities in carcinoma and nonmalignant diseases of the human breast. Br J Cancer 39:681–687PubMedPubMedCentralCrossRefGoogle Scholar
  521. Takahama Y, Yamada Y, Emoto K et al (2002) The prognostic significance of overexpression of the decoy receptor for Fas ligand (DcR3) in patients with gastric carcinomas. Gastric Cancer 5:61–68.  https://doi.org/10.1007/s101200200011CrossRefPubMedPubMedCentralGoogle Scholar
  522. Takahashi K, Yan IK, Haga H, Patel T (2014) Modulation of hypoxia-signaling pathways by extracellular linc-RoR. J Cell Sci 127:1585–1594.  https://doi.org/10.1242/jcs.141069CrossRefPubMedPubMedCentralGoogle Scholar
  523. Takamizawa J, Konishi H, Yanagisawa K et al (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64:3753–3756.  https://doi.org/10.1158/0008-5472.CAN-04-0637CrossRefPubMedPubMedCentralGoogle Scholar
  524. Talos F, Nemajerova A, Flores ER et al (2007) p73 suppresses polyploidy and aneuploidy in the absence of functional p53. Mol Cell 27:647–659.  https://doi.org/10.1016/j.molcel.2007.06.036CrossRefPubMedPubMedCentralGoogle Scholar
  525. Tambe Y, Hasebe M, Kim CJ et al (2016) The drs tumor suppressor regulates glucose metabolism via lactate dehydrogenase-B. Mol Carcinog 55:52–63.  https://doi.org/10.1002/mc.22258CrossRefPubMedPubMedCentralGoogle Scholar
  526. Tarasov V, Jung P, Verdoodt B et al (2007) Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle Georget Tex 6:1586–1593.  https://doi.org/10.4161/cc.6.13.4436CrossRefGoogle Scholar
  527. Tennant DA (2011) PK-M2 makes cells sweeter on HIF1. Cell 145:647–649.  https://doi.org/10.1016/j.cell.2011.05.009CrossRefPubMedPubMedCentralGoogle Scholar
  528. Terry MB, Delgado-Cruzata L, Vin-Raviv N et al (2011) DNA methylation in white blood cells: association with risk factors in epidemiologic studies. Epigenetics 6:828–837PubMedPubMedCentralCrossRefGoogle Scholar
  529. Thomas WD, Zhang XD, Franco AV et al (2000) TNF-related apoptosis-inducing ligand-induced apoptosis of melanoma is associated with changes in mitochondrial membrane potential and perinuclear clustering of mitochondria. J Immunol 165:5612–5620PubMedCrossRefPubMedCentralGoogle Scholar
  530. Tomasetti M, Amati M, Santarelli L, Neuzil J (2016) MicroRNA in metabolic re-programming and their role in tumorigenesis. Int J Mol Sci.  https://doi.org/10.3390/ijms17050754PubMedCentralCrossRefGoogle Scholar
  531. Trabucchi M, Briata P, Garcia-Mayoral M et al (2009) The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature 459:1010–1014.  https://doi.org/10.1038/nature08025CrossRefPubMedPubMedCentralGoogle Scholar
  532. Tsang WP, Ng EKO, Ng SSM et al (2010) Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer. Carcinogenesis 31:350–358.  https://doi.org/10.1093/carcin/bgp181CrossRefPubMedPubMedCentralGoogle Scholar
  533. Tsuji S, Hosotani R, Yonehara S et al (2003) Endogenous decoy receptor 3 blocks the growth inhibition signals mediated by Fas ligand in human pancreatic adenocarcinoma. Int J Cancer 106:17–25.  https://doi.org/10.1002/ijc.11170CrossRefPubMedPubMedCentralGoogle Scholar
  534. Tsutsumi S, Yanagawa T, Shimura T et al (2003) Regulation of cell proliferation by autocrine motility factor/phosphoglucose isomerase signaling. J Biol Chem 278:32165–32172.  https://doi.org/10.1074/jbc.M304537200CrossRefPubMedPubMedCentralGoogle Scholar
  535. Tuncel T, Karagoz B, Haholu A et al (2013) Immunoregulatory function of HLA-G in gastric cancer. Asian Pac J Cancer Prev 14:7681–7684PubMedCrossRefPubMedCentralGoogle Scholar
  536. Uchida C, Miwa S, Kitagawa K et al (2005) Enhanced Mdm2 activity inhibits pRB function via ubiquitin-dependent degradation. EMBO J 24:160–169.  https://doi.org/10.1038/sj.emboj.7600486CrossRefPubMedPubMedCentralGoogle Scholar
  537. Ullah MS, Davies AJ, Halestrap AP (2006) The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1alpha-dependent mechanism. J Biol Chem 281:9030–9037.  https://doi.org/10.1074/jbc.M511397200CrossRefPubMedPubMedCentralGoogle Scholar
  538. Uyttenhove C, Pilotte L, Théate I et al (2003) Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 9:1269–1274.  https://doi.org/10.1038/nm934CrossRefPubMedPubMedCentralGoogle Scholar
  539. Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033.  https://doi.org/10.1126/science.1160809CrossRefPubMedPubMedCentralGoogle Scholar
  540. Venneti S, Dunphy MP, Zhang H et al (2015) Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo. Sci Transl Med 7:274ra17.  https://doi.org/10.1126/scitranslmed.aaa1009CrossRefPubMedPubMedCentralGoogle Scholar
  541. Venteicher AS, Meng Z, Mason PJ et al (2008) Identification of ATPases pontin and reptin as telomerase components essential for holoenzyme assembly. Cell 132:945–957.  https://doi.org/10.1016/j.cell.2008.01.019CrossRefPubMedPubMedCentralGoogle Scholar
  542. Verdun RE, Karlseder J (2006) The DNA damage machinery and homologous recombination pathway act consecutively to protect human telomeres. Cell 127:709–720.  https://doi.org/10.1016/j.cell.2006.09.034CrossRefPubMedPubMedCentralGoogle Scholar
  543. Verdun RE, Karlseder J (2007) Replication and protection of telomeres. Nature 447:924–931.  https://doi.org/10.1038/nature05976CrossRefPubMedPubMedCentralGoogle Scholar
  544. Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ (2011) Natural innate and adaptive immunity to cancer. Annu Rev Immunol 29:235–271.  https://doi.org/10.1146/annurev-immunol-031210-101324CrossRefPubMedPubMedCentralGoogle Scholar
  545. Vidal A, Koff A (2000) Cell-cycle inhibitors: three families united by a common cause. Gene 247:1–15PubMedCrossRefPubMedCentralGoogle Scholar
  546. Vinagre J, Almeida A, Pópulo H et al (2013) Frequency of TERT promoter mutations in human cancers. Nat Commun 4:2185.  https://doi.org/10.1038/ncomms3185CrossRefPubMedPubMedCentralGoogle Scholar
  547. Vinay DS, Ryan EP, Pawelec G et al (2015) Immune evasion in cancer: mechanistic basis and therapeutic strategies. Semin Cancer Biol 35(Suppl):S185–S198.  https://doi.org/10.1016/j.semcancer.2015.03.004CrossRefPubMedPubMedCentralGoogle Scholar
  548. Vincent K, Pichler M, Lee G-W, Ling H (2014) MicroRNAs, genomic instability and cancer. Int J Mol Sci 15:14475–14491.  https://doi.org/10.3390/ijms150814475CrossRefPubMedPubMedCentralGoogle Scholar
  549. Viswanathan SR, Daley GQ, Gregory RI (2008) Selective blockade of microRNA processing by Lin28. Science 320:97–100.  https://doi.org/10.1126/science.1154040CrossRefPubMedPubMedCentralGoogle Scholar
  550. Vulliamy T, Beswick R, Kirwan M et al (2008) Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita. Proc Natl Acad Sci U S A 105:8073–8078.  https://doi.org/10.1073/pnas.0800042105CrossRefPubMedPubMedCentralGoogle Scholar
  551. Walter M, Teissandier A, Pérez-Palacios R, Bourc’his D (2016) An epigenetic switch ensures transposon repression upon dynamic loss of DNA methylation in embryonic stem cells. elife.  https://doi.org/10.7554/eLife.11418
  552. Wan G, Mathur R, Hu X et al (2013) Long non-coding RNA ANRIL (CDKN2B-AS) is induced by the ATM-E2F1 signaling pathway. Cell Signal 25:1086–1095.  https://doi.org/10.1016/j.cellsig.2013.02.006CrossRefPubMedPubMedCentralGoogle Scholar
  553. Wan G, Liu Y, Han C et al (2014) Noncoding RNAs in DNA repair and genome integrity. Antioxid Redox Signal 20:655–677.  https://doi.org/10.1089/ars.2013.5514CrossRefPubMedPubMedCentralGoogle Scholar
  554. Wang X, Arai S, Song X et al (2008) Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature 454:126–130.  https://doi.org/10.1038/nature06992CrossRefPubMedPubMedCentralGoogle Scholar
  555. Wang J, Liu X, Wu H et al (2010) CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res 38:5366–5383.  https://doi.org/10.1093/nar/gkq285CrossRefPubMedPubMedCentralGoogle Scholar
  556. Wang Y, Wang Y, Shen L et al (2012) Prognostic and therapeutic implications of increased ATP citrate lyase expression in human epithelial ovarian cancer. Oncol Rep 27:1156–1162.  https://doi.org/10.3892/or.2012.1638CrossRefPubMedPubMedCentralGoogle Scholar
  557. Wang J, He J, Su F et al (2013a) Repression of ATR pathway by miR-185 enhances radiation-induced apoptosis and proliferation inhibition. Cell Death Dis 4:e699.  https://doi.org/10.1038/cddis.2013.227CrossRefPubMedPubMedCentralGoogle Scholar
  558. Wang W, Li F, Mao Y et al (2013b) A miR-570 binding site polymorphism in the B7-H1 gene is associated with the risk of gastric adenocarcinoma. Hum Genet 132:641–648.  https://doi.org/10.1007/s00439-013-1275-6CrossRefPubMedPubMedCentralGoogle Scholar
  559. Wang W, Ren F, Wu Q et al (2014) MicroRNA-497 suppresses angiogenesis by targeting vascular endothelial growth factor A through the PI3K/AKT and MAPK/ERK pathways in ovarian cancer. Oncol Rep 32:2127–2133.  https://doi.org/10.3892/or.2014.3439CrossRefPubMedPubMedCentralGoogle Scholar
  560. Wang Q, Hardie R-A, Hoy AJ et al (2015a) Targeting ASCT2-mediated glutamine uptake blocks prostate cancer growth and tumour development. J Pathol 236:278–289.  https://doi.org/10.1002/path.4518CrossRefPubMedPubMedCentralGoogle Scholar
  561. Wang W, Zhang E, Lin C (2015b) MicroRNAs in tumor angiogenesis. Life Sci 136:28–35.  https://doi.org/10.1016/j.lfs.2015.06.025CrossRefPubMedPubMedCentralGoogle Scholar
  562. Wang X, Li J, Dong K et al (2015c) Tumor suppressor miR-34a targets PD-L1 and functions as a potential immunotherapeutic target in acute myeloid leukemia. Cell Signal 27:443–452.  https://doi.org/10.1016/j.cellsig.2014.12.003CrossRefPubMedPubMedCentralGoogle Scholar
  563. Warburg O (1956a) On the origin of cancer cells. Science 123:309–314CrossRefGoogle Scholar
  564. Warburg O (1956b) On respiratory impairment in cancer cells. Science 124:269–270PubMedPubMedCentralGoogle Scholar
  565. Warburg O, Wind F, Negelein E (1927) The metabolism of tumors in the body. J Gen Physiol 8:519–530PubMedPubMedCentralCrossRefGoogle Scholar
  566. Ward PS, Thompson CB (2012) Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 21:297–308.  https://doi.org/10.1016/j.ccr.2012.02.014CrossRefPubMedPubMedCentralGoogle Scholar
  567. Watanabe H, Carmi P, Hogan V et al (1991) Purification of human tumor cell autocrine motility factor and molecular cloning of its receptor. J Biol Chem 266:13442–13448PubMedPubMedCentralGoogle Scholar
  568. Watson JD (1972) Origin of concatemeric T7 DNA. Nat New Biol 239:197–201PubMedCrossRefPubMedCentralGoogle Scholar
  569. Wei Z, Cui L, Mei Z et al (2014) miR-181a mediates metabolic shift in colon cancer cells via the PTEN/AKT pathway. FEBS Lett 588:1773–1779.  https://doi.org/10.1016/j.febslet.2014.03.037CrossRefPubMedPubMedCentralGoogle Scholar
  570. Wei J, Nduom EK, Kong L-Y et al (2016) MiR-138 exerts anti-glioma efficacy by targeting immune checkpoints. Neuro-Oncol 18:639–648.  https://doi.org/10.1093/neuonc/nov292CrossRefPubMedPubMedCentralGoogle Scholar
  571. Weinberg RA (1995) The retinoblastoma protein and cell cycle control. Cell 81:323–330PubMedCrossRefPubMedCentralGoogle Scholar
  572. Weinhouse S (1956) On respiratory impairment in cancer cells. Science 124:267–269PubMedCrossRefPubMedCentralGoogle Scholar
  573. Weinhouse S (1976) The Warburg hypothesis fifty years later. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 87:115–126PubMedCrossRefPubMedCentralGoogle Scholar
  574. Weinhouse S, Millington RH, Wenner CE (1951) Metabolism of neoplastic tissue. I. The oxidation of carbohydrate and fatty acids in transplanted tumors. Cancer Res 11:845–850PubMedPubMedCentralGoogle Scholar
  575. Welford SM, Giaccia AJ (2011) Hypoxia and senescence: the impact of oxygenation on tumor suppression. Mol Cancer Res 9:538–544.  https://doi.org/10.1158/1541-7786.MCR-11-0065CrossRefPubMedPubMedCentralGoogle Scholar
  576. Wellen KE, Lu C, Mancuso A et al (2010) The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. Genes Dev 24:2784–2799.  https://doi.org/10.1101/gad.1985910CrossRefPubMedPubMedCentralGoogle Scholar
  577. White MK, Pagano JS, Khalili K (2014) Viruses and human cancers: a long road of discovery of molecular paradigms. Clin Microbiol Rev 27:463–481.  https://doi.org/10.1128/CMR.00124-13CrossRefPubMedPubMedCentralGoogle Scholar
  578. Whiteside TL, Herberman RB (1995) The role of natural killer cells in immune surveillance of cancer. Curr Opin Immunol 7:704–710PubMedCrossRefPubMedCentralGoogle Scholar
  579. Wise DR, Thompson CB (2010) Glutamine addiction: a new therapeutic target in cancer. Trends Biochem Sci 35:427–433.  https://doi.org/10.1016/j.tibs.2010.05.003CrossRefPubMedPubMedCentralGoogle Scholar
  580. Wong RSY (2011) Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res CR 30:87.  https://doi.org/10.1186/1756-9966-30-87CrossRefPubMedPubMedCentralGoogle Scholar
  581. Wong K-K, Engelman JA, Cantley LC (2010) Targeting the PI3K signaling pathway in cancer. Curr Opin Genet Dev 20:87–90.  https://doi.org/10.1016/j.gde.2009.11.002CrossRefPubMedPubMedCentralGoogle Scholar
  582. Wu KJ, Grandori C, Amacker M et al (1999) Direct activation of TERT transcription by c-MYC. Nat Genet 21:220–224.  https://doi.org/10.1038/6010CrossRefPubMedPubMedCentralGoogle Scholar
  583. Wu L, Chen Z, Zhang J, Xing Y (2012) Effect of miR-513a-5p on etoposide-stimulating B7-H1 expression in retinoblastoma cells. J Huazhong Univ Sci Technol Med Sci Hua Zhong Ke Ji Xue Xue Bao Yi Xue Ying Wen Ban Huazhong Keji Daxue Xuebao Yixue Yingdewen Ban 32:601–606.  https://doi.org/10.1007/s11596-012-1004-8CrossRefGoogle Scholar
  584. Wu C-W, Dong Y-J, Liang Q-Y et al (2013a) MicroRNA-18a attenuates DNA damage repair through suppressing the expression of ataxia telangiectasia mutated in colorectal cancer. PLoS One 8:e57036.  https://doi.org/10.1371/journal.pone.0057036CrossRefPubMedPubMedCentralGoogle Scholar
  585. Wu X, Li Y, Wang J et al (2013b) Long chain fatty Acyl-CoA synthetase 4 is a biomarker for and mediator of hormone resistance in human breast cancer. PLoS One 8:e77060.  https://doi.org/10.1371/journal.pone.0077060CrossRefPubMedPubMedCentralGoogle Scholar
  586. Xia H, Ooi LLPJ, Hui KM (2013) MicroRNA-216a/217-induced epithelial-mesenchymal transition targets PTEN and SMAD7 to promote drug resistance and recurrence of liver cancer. Hepatology 58:629–641.  https://doi.org/10.1002/hep.26369CrossRefPubMedPubMedCentralGoogle Scholar
  587. Xiao C, Srinivasan L, Calado DP et al (2008) Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol 9:405–414.  https://doi.org/10.1038/ni1575CrossRefPubMedPubMedCentralGoogle Scholar
  588. Xiao J, Lin H, Luo X et al (2011) miR-605 joins p53 network to form a p53:miR-605:Mdm2 positive feedback loop in response to stress. EMBO J 30:524–532.  https://doi.org/10.1038/emboj.2010.347CrossRefPubMedPubMedCentralGoogle Scholar
  589. Xu Y, Kimura T, Komiyama M (2008) Human telomere RNA and DNA form an intermolecular G-quadruplex. Nucleic Acids Symp Ser 2004:169–170.  https://doi.org/10.1093/nass/nrn086CrossRefGoogle Scholar
  590. Xu Y, Suzuki Y, Ito K, Komiyama M (2010) Telomeric repeat-containing RNA structure in living cells. Proc Natl Acad Sci U S A 107:14579–14584.  https://doi.org/10.1073/pnas.1001177107CrossRefPubMedPubMedCentralGoogle Scholar
  591. Xu Q, Liu L-Z, Qian X et al (2012) MiR-145 directly targets p70S6K1 in cancer cells to inhibit tumor growth and angiogenesis. Nucleic Acids Res 40:761–774.  https://doi.org/10.1093/nar/gkr730CrossRefPubMedPubMedCentralGoogle Scholar
  592. Xu H, Zhu J, Hu C et al (2016a) Inhibition of microRNA-181a may suppress proliferation and invasion and promote apoptosis of cervical cancer cells through the PTEN/Akt/FOXO1 pathway. J Physiol Biochem 72:721–732.  https://doi.org/10.1007/s13105-016-0511-7CrossRefPubMedPubMedCentralGoogle Scholar
  593. Xu S, Tao Z, Hai B et al (2016b) miR-424(322) reverses chemoresistance via T-cell immune response activation by blocking the PD-L1 immune checkpoint. Nat Commun 7:11406.  https://doi.org/10.1038/ncomms11406CrossRefPubMedPubMedCentralGoogle Scholar
  594. Yamakuchi M, Lotterman CD, Bao C et al (2010) P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis. Proc Natl Acad Sci U S A 107:6334–6339.  https://doi.org/10.1073/pnas.0911082107CrossRefPubMedPubMedCentralGoogle Scholar
  595. Yan S, Yang X-F, Liu H-L et al (2015) Long-chain acyl-CoA synthetase in fatty acid metabolism involved in liver and other diseases: an update. World J Gastroenterol 21:3492–3498.  https://doi.org/10.3748/wjg.v21.i12.3492CrossRefPubMedPubMedCentralGoogle Scholar
  596. Yanaihara N, Caplen N, Bowman E et al (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9:189–198.  https://doi.org/10.1016/j.ccr.2006.01.025CrossRefPubMedGoogle Scholar
  597. Yang Y-G, Qi Y (2015) RNA-directed repair of DNA double-strand breaks. DNA Repair 32:82–85.  https://doi.org/10.1016/j.dnarep.2015.04.017CrossRefPubMedGoogle Scholar
  598. Yang Y-A, Han WF, Morin PJ et al (2002) Activation of fatty acid synthesis during neoplastic transformation: role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Exp Cell Res 279:80–90PubMedCrossRefGoogle Scholar
  599. Yang H, Kong W, He L et al (2008) MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res 68:425–433.  https://doi.org/10.1158/0008-5472.CAN-07-2488CrossRefPubMedGoogle Scholar
  600. Yang C, Sudderth J, Dang T et al (2009) Glioblastoma cells require glutamate dehydrogenase to survive impairments of glucose metabolism or Akt signaling. Cancer Res 69:7986–7993.  https://doi.org/10.1158/0008-5472.CAN-09-2266CrossRefPubMedPubMedCentralGoogle Scholar
  601. Yang F, Zhang L, Huo X et al (2011) Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology 54:1679–1689.  https://doi.org/10.1002/hep.24563CrossRefPubMedGoogle Scholar
  602. Yang Y, Sun M, Wang L, Jiao B (2013) HIFs, angiogenesis, and cancer. J Cell Biochem 114:967–974.  https://doi.org/10.1002/jcb.24438CrossRefPubMedPubMedCentralGoogle Scholar
  603. Yang F, Zhang H, Mei Y, Wu M (2014) Reciprocal regulation of HIF-1α and lincRNA-p21 modulates the Warburg effect. Mol Cell 53:88–100.  https://doi.org/10.1016/j.molcel.2013.11.004CrossRefPubMedPubMedCentralGoogle Scholar
  604. Yap KL, Li S, Muñoz-Cabello AM et al (2010) Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell 38:662–674.  https://doi.org/10.1016/j.molcel.2010.03.021CrossRefPubMedPubMedCentralGoogle Scholar
  605. Yeager TR, Neumann AA, Englezou A et al (1999) Telomerase-negative immortalized human cells contain a novel type of promyelocytic leukemia (PML) body. Cancer Res 59:4175–4179PubMedPubMedCentralGoogle Scholar
  606. Yehezkel S, Segev Y, Viegas-Péquignot E et al (2008) Hypomethylation of subtelomeric regions in ICF syndrome is associated with abnormally short telomeres and enhanced transcription from telomeric regions. Hum Mol Genet 17:2776–2789.  https://doi.org/10.1093/hmg/ddn177CrossRefPubMedPubMedCentralGoogle Scholar
  607. Yi X, Tesmer VM, Savre-Train I et al (1999) Both transcriptional and posttranscriptional mechanisms regulate human telomerase template RNA levels. Mol Cell Biol 19:3989–3997PubMedPubMedCentralCrossRefGoogle Scholar
  608. Yi X, Yin X-M, Dong Z (2003) Inhibition of Bid-induced apoptosis by Bcl-2. tBid insertion, Bax translocation, and Bax/Bak oligomerization suppressed. J Biol Chem 278:16992–16999.  https://doi.org/10.1074/jbc.M300039200CrossRefPubMedPubMedCentralGoogle Scholar
  609. Yin L, Hubbard AK, Giardina C (2000) NF-kappa B regulates transcription of the mouse telomerase catalytic subunit. J Biol Chem 275:36671–36675.  https://doi.org/10.1074/jbc.M007378200CrossRefPubMedPubMedCentralGoogle Scholar
  610. Yin Y, Cai X, Chen X et al (2014) Tumor-secreted miR-214 induces regulatory T cells: a major link between immune evasion and tumor growth. Cell Res 24:1164–1180.  https://doi.org/10.1038/cr.2014.121CrossRefPubMedPubMedCentralGoogle Scholar
  611. Yoon S, Lee M-Y, Park SW et al (2007) Up-regulation of acetyl-CoA carboxylase alpha and fatty acid synthase by human epidermal growth factor receptor 2 at the translational level in breast cancer cells. J Biol Chem 282:26122–26131.  https://doi.org/10.1074/jbc.M702854200CrossRefPubMedPubMedCentralGoogle Scholar
  612. Yoshida GJ (2015) Metabolic reprogramming: the emerging concept and associated therapeutic strategies. J Exp Clin Cancer Res CR 34:111.  https://doi.org/10.1186/s13046-015-0221-yCrossRefPubMedPubMedCentralGoogle Scholar
  613. Yoshida M, Miyoshi I, Hinuma Y (1982) Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. Proc Natl Acad Sci U S A 79:2031–2035PubMedPubMedCentralCrossRefGoogle Scholar
  614. Yu H, Kortylewski M, Pardoll D (2007) Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol 7:41–51.  https://doi.org/10.1038/nri1995CrossRefPubMedPubMedCentralGoogle Scholar
  615. Yu W, Gius D, Onyango P et al (2008) Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature 451:202–206.  https://doi.org/10.1038/nature06468CrossRefPubMedPubMedCentralGoogle Scholar
  616. Yu T-Y, Kao Y, Lin J-J (2014) Telomeric transcripts stimulate telomere recombination to suppress senescence in cells lacking telomerase. Proc Natl Acad Sci U S A 111:3377–3382.  https://doi.org/10.1073/pnas.1307415111CrossRefPubMedPubMedCentralGoogle Scholar
  617. Yu C, Xue J, Zhu W et al (2015) Warburg meets non-coding RNAs: the emerging role of ncRNA in regulating the glucose metabolism of cancer cells. Tumour Biol 36:81–94.  https://doi.org/10.1007/s13277-014-2875-zCrossRefPubMedPubMedCentralGoogle Scholar
  618. Yu L, Chen X, Wang L, Chen S (2016) The sweet trap in tumors: aerobic glycolysis and potential targets for therapy. Oncotarget 7:38908–38926.  https://doi.org/10.18632/oncotarget.7676CrossRefPubMedPubMedCentralGoogle Scholar
  619. Yue S, Li J, Lee S-Y et al (2014) Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab 19:393–406.  https://doi.org/10.1016/j.cmet.2014.01.019CrossRefPubMedPubMedCentralGoogle Scholar
  620. Zaugg K, Yao Y, Reilly PT et al (2011) Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress. Genes Dev 25:1041–1051.  https://doi.org/10.1101/gad.1987211CrossRefPubMedPubMedCentralGoogle Scholar
  621. Zee Y-K, O’Connor JPB, Parker GJM et al (2010) Imaging angiogenesis of genitourinary tumors. Nat Rev Urol 7:69–82.  https://doi.org/10.1038/nrurol.2009.262CrossRefPubMedPubMedCentralGoogle Scholar
  622. Zhai H, Fesler A, Ju J (2013) MicroRNA: a third dimension in autophagy. Cell Cycle Georget Tex 12:246–250.  https://doi.org/10.4161/cc.23273CrossRefGoogle Scholar
  623. Zhang C, Peng G (2015) Non-coding RNAs: an emerging player in DNA damage response. Mutat Res Rev Mutat Res 763:202–211.  https://doi.org/10.1016/j.mrrev.2014.11.003CrossRefPubMedPubMedCentralGoogle Scholar
  624. Zhang W, Patil S, Chauhan B et al (2006) FoxO1 regulates multiple metabolic pathways in the liver: effects on gluconeogenic, glycolytic, and lipogenic gene expression. J Biol Chem 281:10105–10117.  https://doi.org/10.1074/jbc.M600272200CrossRefPubMedPubMedCentralGoogle Scholar
  625. Zhang H, Bosch-Marce M, Shimoda LA et al (2008) Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem 283:10892–10903.  https://doi.org/10.1074/jbc.M800102200CrossRefPubMedPubMedCentralGoogle Scholar
  626. Zhang X, Wan G, Mlotshwa S et al (2010) Oncogenic Wip1 phosphatase is inhibited by miR-16 in the DNA damage signaling pathway. Cancer Res 70:7176–7186.  https://doi.org/10.1158/0008-5472.CAN-10-0697CrossRefPubMedPubMedCentralGoogle Scholar
  627. Zhang X, Wan G, Berger FG et al (2011) The ATM kinase induces microRNA biogenesis in the DNA damage response. Mol Cell 41:371–383.  https://doi.org/10.1016/j.molcel.2011.01.020CrossRefPubMedPubMedCentralGoogle Scholar
  628. Zhang Y, Toh L, Lau P, Wang X (2012) Human telomerase reverse transcriptase (hTERT) is a novel target of the Wnt/β-catenin pathway in human cancer. J Biol Chem 287:32494–32511.  https://doi.org/10.1074/jbc.M112.368282CrossRefPubMedPubMedCentralGoogle Scholar
  629. Zhang J, Sun Q, Zhang Z et al (2013a) Loss of microRNA-143/145 disturbs cellular growth and apoptosis of human epithelial cancers by impairing the MDM2-p53 feedback loop. Oncogene 32:61–69.  https://doi.org/10.1038/onc.2012.28CrossRefPubMedPubMedCentralGoogle Scholar
  630. Zhang Y, Wang X, Xu B et al (2013b) Epigenetic silencing of miR-126 contributes to tumor invasion and angiogenesis in colorectal cancer. Oncol Rep 30:1976–1984.  https://doi.org/10.3892/or.2013.2633CrossRefPubMedPubMedCentralGoogle Scholar
  631. Zhang A, Xu M, Mo Y-Y (2014a) Role of the lncRNA-p53 regulatory network in cancer. J Mol Cell Biol 6:181–191.  https://doi.org/10.1093/jmcb/mju013CrossRefPubMedPubMedCentralGoogle Scholar
  632. Zhang X, Nie Y, Li X et al (2014b) MicroRNA-181a functions as an oncomir in gastric cancer by targeting the tumour suppressor gene ATM. Pathol Oncol Res 20:381–389.  https://doi.org/10.1007/s12253-013-9707-0CrossRefPubMedPubMedCentral