Noncoding RNAs in Growth and Death of Cancer Cells

  • Anfei Liu
  • Shanrong LiuEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 927)


The mammalian genomes are mostly comprised of noncoding genes. And mammalian genomes are characterized by pervasive expression of different types of noncoding RNAs (ncRNAs). In sharp contrast to previous collections, these ncRNAs show strong purifying selection evolutionary conservation. Previous studies indicated that only a small fraction of the mammalian genome codes for messenger RNAs destined to be translated into peptides or proteins, and it is generally assumed that a large portion of transcribed sequences—including pseudogenes and several classes of ncRNAs—do not give rise to peptides or proteins. However, ribosome profiling suggests that ribosomes occupy many regions of the transcriptome thought to be noncoding. Moreover, these observations highlight a potentially large and complex set of biologically regulated translational events from transcripts formerly thought to lack coding potential. Furthermore, accumulating evidence from previous studies has suggested that the novel translation products exhibit temporal regulation similar to that of proteins known to be involved in many biological activity processes. In this review, we focus on the coding potential of noncoding genes and ncRNAs. We also sketched the possible mechanisms for their coding activities. Overall, our review provides new insights into the word of central dogma and is an expansive resource of functional annotations for biomedical research. At last, the outcome of the majority of the translation events and their potential biological purpose remain an intriguing topic for future investigation.


Cancer cells Noncoding RNA Proliferation Cell cycle Necrosis Apoptosis Autophagy 


  1. 1.
    Fu XD. Non-coding RNA: a new frontier in regulatory biology. Natl Sci Rev. 2014;1(2):190–204. doi: 10.1093/nsr/nwu008.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Tordonato C, Di Fiore PP, Nicassio F. The role of non-coding RNAs in the regulation of stem cells and progenitors in the normal mammary gland and in breast tumors. Front Genet. 2015;6:72. doi: 10.3389/fgene.2015.00072.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Hah N, Danko CG, Core L, et al. A rapid, extensive, and transient transcriptional response to estrogen signaling in breast cancer cells. Cell. 2011;145(4):622–34. doi: 10.1016/j.cell.2011.03.042.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Cui P, Lin Q, Ding F, et al. A comparison between ribo-minus RNA-sequencing and polyA-selected RNA-sequencing. Genomics. 2010;96(5):259–65. doi: 10.1016/j.ygeno.2010.07.010.PubMedCrossRefGoogle Scholar
  5. 5.
    Yang L, Lin C, Jin C, et al. lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs. Nature. 2013;500(7464):598–602. doi: 10.1038/nature12451.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Kowalczykiewic D, Wrzesinski J. The role of piRNA and Piwi proteins in regulation of germline development. Postepy Biochem. 2011;57(3):249–56.PubMedGoogle Scholar
  7. 7.
    Hon GC, Hawkins RD, Caballero OL, et al. Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer. Genome Res. 2012;22(2):246–58. doi: 10.1101/gr.125872.111.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Hervouet E, Cartron PF, Jouvenot M, Delage-Mourroux R. Epigenetic regulation of estrogen signaling in breast cancer. Epigenetics. 2013;8(3):237–45. doi: 10.4161/epi.23790.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Zhang C, Peng G. Non-coding RNAs: an emerging player in DNA damage response. Mutat Res Rev Mutat Res. 2015;763:202–11. doi: 10.1016/j.mrrev.2014.11.003.PubMedCrossRefGoogle Scholar
  10. 10.
    Li Y, Zhang Y, Li S, et al. Genome-wide DNA methylome analysis reveals epigenetically dysregulated non-coding RNAs in human breast cancer. Sci Rep. 2015;5:8790. doi: 10.1038/srep08790.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Yan Y, Shen Z, Gao Z, et al. LncRNA specific for distant metastasis of gastric cancer is associated with TRIM16 expression and facilitates tumor cell invasion in vitro. J Gastroenterol Hepatol. 2015;30:1367–75. doi: 10.1111/jgh.12976.PubMedCrossRefGoogle Scholar
  12. 12.
    Lu T, Shao N, Ji C. Targeting microRNAs to modulate TRAIL-induced apoptosis of cancer cells. Cancer Gene Ther. 2013;20(1):33–7. doi: 10.1038/cgt.2012.81.PubMedCrossRefGoogle Scholar
  13. 13.
    Shi X, Sun M, Wu Y, et al. Post-transcriptional regulation of long non-coding RNAs in cancer. Tumour Biol. 2015;36(2):503–13. doi: 10.1007/s13277-015-3106-y.PubMedCrossRefGoogle Scholar
  14. 14.
    Bhan A, Mandal SS. Long non-coding RNAs: emerging stars in gene regulation, epigenetics and human disease. ChemMedChem. 2014;9(9):1932–56. doi: 10.1002/cmdc.201300534.PubMedCrossRefGoogle Scholar
  15. 15.
    Seth S, Johns R, Templin MV. Delivery and biodistribution of siRNA for cancer therapy: challenges and future prospects. Ther Deliv. 2012;3(2):245–61.PubMedCrossRefGoogle Scholar
  16. 16.
    Qiao D, Zeeman AM, Deng W, Looijenga LH, Lin H. Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene. 2002;21(25):3988–99. doi: 10.1038/sj.onc.1205505.PubMedCrossRefGoogle Scholar
  17. 17.
    Liu X, Sun Y, Guo J, et al. Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells. Int J Cancer. 2006;118(8):1922–9. doi: 10.1002/ijc.21575.PubMedCrossRefGoogle Scholar
  18. 18.
    Liu JJ, Shen R, Chen L, et al. Piwil2 is expressed in various stages of breast cancers and has the potential to be used as a novel biomarker. Int J Clin Exp Pathol. 2010;3(4):328–37.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Lim SL, Ricciardelli C, Oehler MK, et al. Overexpression of piRNA pathway genes in epithelial ovarian cancer. PLoS One. 2014;9(6), e99687. doi: 10.1371/journal.pone.0099687.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Plosky BS. eRNAs lure NELF from paused polymerases. Mol Cell. 2014;56(1):3–4. doi: 10.1016/j.molcel.2014.09.016.PubMedCrossRefGoogle Scholar
  21. 21.
    Artandi SE, DePinho RA. Telomeres and telomerase in cancer. Carcinogenesis. 2010;31(1):9–18. doi: 10.1093/carcin/bgp268.PubMedCrossRefGoogle Scholar
  22. 22.
    Hansen TB, Kjems J, Damgaard CK. Circular RNA and miR-7 in cancer. Cancer Res. 2013;73(18):5609–12. doi: 10.1158/0008-5472.CAN-13-1568.PubMedCrossRefGoogle Scholar
  23. 23.
    Schmidt U, Keck ME, Buell DR. miRNAs and other non-coding RNAs in posttraumatic stress disorder: A systematic review of clinical and animal studies. J Psychiatr Res. 2015;65:1–8. doi: 10.1016/j.jpsychires.2015.03.014.PubMedCrossRefGoogle Scholar
  24. 24.
    Malumbres M. miRNAs and cancer: an epigenetics view. Mol Aspects Med. 2013;34(4):863–74. doi: 10.1016/j.mam.2012.06.005.PubMedCrossRefGoogle Scholar
  25. 25.
    Esquela-Kerscher A, Slack FJ. Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69. doi: 10.1038/nrc1840.PubMedCrossRefGoogle Scholar
  26. 26.
    Sanchez-Mejias A, Tay Y. Competing endogenous RNA networks: tying the essential knots for cancer biology and therapeutics. J Hematol Oncol. 2015;8(1):30. doi: 10.1186/s13045-015-0129-1.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Feitelson MA, Arzumanyan A, Kulathinal RJ, et al. Sustained proliferation in cancer: mechanisms and novel therapeutic targets. Semin Cancer Biol. 2015;35:S25–54. doi: 10.1016/j.semcancer.2015.02.006.PubMedCrossRefGoogle Scholar
  28. 28.
    Zheng W, Liu Z, Zhang W, Hu X. miR-31 functions as an oncogene in cervical cancer. Arch Gynecol Obstet. 2015;292:1083–9. doi: 10.1007/s00404-015-3713-2.PubMedCrossRefGoogle Scholar
  29. 29.
    Li R, Shi X, Ling F, et al. MiR-34a suppresses ovarian cancer proliferation and motility by targeting AXL. Tumour Biol. 2015;36:7277–83. doi: 10.1007/s13277-015-3445-8.PubMedCrossRefGoogle Scholar
  30. 30.
    Xu M, Gu M, Zhang K, et al. miR-203 inhibition of renal cancer cell proliferation, migration and invasion by targeting of FGF2. Diagn Pathol. 2015;10(1):24. doi: 10.1186/s13000-015-0255-7.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Yang X, Chen BB, Zhang MH, Wang XR. MicroRNA-126 inhibits the proliferation of lung cancer cell line A549. Asian Pac J Trop Med. 2015;8(3):239–42. doi: 10.1016/S1995-7645(14)60323-0.PubMedCrossRefGoogle Scholar
  32. 32.
    Rebucci M, Sermeus A, Leonard E, et al. miRNA-196b inhibits cell proliferation and induces apoptosis in HepG2 cells by targeting IGF2BP1. Mol Cancer. 2015;14(1):79. doi: 10.1186/s12943-015-0349-6.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Chen F, Hu SJ. Effect of microRNA-34a in cell cycle, differentiation, and apoptosis: a review. J Biochem Mol Toxicol. 2012;26(2):79–86. doi: 10.1002/jbt.20412.PubMedCrossRefGoogle Scholar
  34. 34.
    Schafer KA. The cell cycle: a review. Vet Pathol. 1998;35(6):461–78.PubMedCrossRefGoogle Scholar
  35. 35.
    Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009;9(3):153–66. doi: 10.1038/nrc2602.PubMedCrossRefGoogle Scholar
  36. 36.
    Kim HS, Lee KS, Bae HJ, et al. MicroRNA-31 functions as a tumor suppressor by regulating cell cycle and epithelial-mesenchymal transition regulatory proteins in liver cancer. Oncotarget. 2015;6(10):8089–102.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Lin Y, Li D, Liang Q, et al. miR-638 regulates differentiation and proliferation in leukemic cells by targeting cyclin-dependent kinase 2. J Biol Chem. 2015;290(3):1818–28. doi: 10.1074/jbc.M114.599191.PubMedCrossRefGoogle Scholar
  38. 38.
    Li LP, Wu WJ, Sun DY, et al. miR-449a and CDK6 in gastric carcinoma. Oncol Lett. 2014;8(4):1533–8. doi: 10.3892/ol.2014.2370.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Zhao Z, Ma X, Sung D, et al. microRNA-449a functions as a tumor suppressor in neuroblastoma through inducing cell differentiation and cell cycle arrest. RNA Biol. 2015;12(5):538–54. doi: 10.1080/15476286.2015.1023495.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Chen W, Qi J, Bao G, et al. Emerging role of microRNA-27a in human malignant glioma cell survival via targeting of prohibitin. Mol Med Rep. 2015;12(1):1515–23. doi: 10.3892/mmr.2015.3475.PubMedGoogle Scholar
  41. 41.
    Ouyang L, Shi Z, Zhao S, et al. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif. 2012;45(6):487–98. doi: 10.1111/j.1365-2184.2012.00845.x.PubMedCrossRefGoogle Scholar
  42. 42.
    Shivapurkar N, Reddy J, Chaudhary PM, Gazdar AF. Apoptosis and lung cancer: a review. J Cell Biochem. 2003;88(5):885–98. doi: 10.1002/jcb.10440.PubMedCrossRefGoogle Scholar
  43. 43.
    Su Z, Yang Z, Xu Y, et al. MicroRNAs in apoptosis, autophagy and necroptosis. Oncotarget. 2015;6(11):8474–90.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Wang H, Li J, Chi H, et al. MicroRNA-181c targets Bcl-2 and regulates mitochondrial morphology in myocardial cells. J Cell Mol Med. 2015;19:2084–97. doi: 10.1111/jcmm.12563.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Zhang Y, Schiff D, Park D, Abounader R. MicroRNA-608 and microRNA-34a regulate chordoma malignancy by targeting EGFR, Bcl-xL and MET. PLoS One. 2014;9(3), e91546. doi: 10.1371/journal.pone.0091546.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Ji F, Zhang H, Wang Y, et al. MicroRNA-133a, down-regulated in osteosarcoma, suppresses proliferation and promotes apoptosis by targeting Bcl-xL and Mcl-1. Bone. 2013;56(1):220–6. doi: 10.1016/j.bone.2013.05.020.PubMedCrossRefGoogle Scholar
  47. 47.
    Lou G, Liu Y, Wu S, et al. The p53/miR-34a/SIRT1 Positive Feedback Loop in Quercetin-Induced Apoptosis. Cell Physiol Biochem. 2015;35(6):2192–202. doi: 10.1159/000374024.PubMedCrossRefGoogle Scholar
  48. 48.
    Huang G, Nishimoto K, Zhou Z, et al. miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating Fas expression. Cancer Res. 2012;72(4):908–16. doi: 10.1158/0008-5472.CAN-11-1460.PubMedCrossRefGoogle Scholar
  49. 49.
    Xie X, Hu Y, Xu L, et al. The role of miR-125b-mitochondria-caspase-3 pathway in doxorubicin resistance and therapy in human breast cancer. Tumour Biol. 2015;36:7185–94. doi: 10.1007/s13277-015-3438-7.PubMedCrossRefGoogle Scholar
  50. 50.
    Ihle MA, Trautmann M, Kuenstlinger H, et al. miRNA-221 and miRNA-222 induce apoptosis via the KIT/AKT signalling pathway in gastrointestinal stromal tumours. Mol Oncol. 2015;9:1421–33. doi: 10.1016/j.molonc.2015.03.013.PubMedCrossRefGoogle Scholar
  51. 51.
    Su Z, Yang Z, Xu Y, et al. Apoptosis, autophagy, necroptosis, and cancer metastasis. Mol Cancer. 2015;14(1):48. doi: 10.1186/s12943-015-0321-5.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Petersen SL, Chen TT, Lawrence DA, et al. TRAF2 is a biologically important necroptosis suppressor. Cell Death Differ. 2015;22:1846–57. doi: 10.1038/cdd.2015.35.PubMedCrossRefGoogle Scholar
  53. 53.
    Liu J, van Mil A, Vrijsen K, et al. MicroRNA-155 prevents necrotic cell death in human cardiomyocyte progenitor cells via targeting RIP1. J Cell Mol Med. 2011;15(7):1474–82. doi: 10.1111/j.1582-4934.2010.01104.x.PubMedCrossRefGoogle Scholar
  54. 54.
    Wang K, Liu F, Zhou LY, et al. miR-874 regulates myocardial necrosis by targeting caspase-8. Cell Death Dis. 2013;4:e709. doi: 10.1038/cddis.2013.233.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Rebecca VW, Amaravadi RK. Emerging strategies to effectively target autophagy in cancer. Oncogene. 2016;35:1–11. doi: 10.1038/onc.2015.99.PubMedCrossRefGoogle Scholar
  56. 56.
    Lu C, Chen J, Xu HG, et al. MIR106B and MIR93 prevent removal of bacteria from epithelial cells by disrupting ATG16L1-mediated autophagy. Gastroenterology. 2014;146(1):188–99. doi: 10.1053/j.gastro.2013.09.006.PubMedCrossRefGoogle Scholar
  57. 57.
    Zheng B, Zhu H, Gu D, Pan X, et al. MiRNA-30a-mediated autophagy inhibition sensitizes renal cell carcinoma cells to sorafenib. Biochem Biophys Res Commun. 2015;459(2):234–9. doi: 10.1016/j.bbrc.2015.02.084.PubMedCrossRefGoogle Scholar
  58. 58.
    Chang Y, Yan W, He X, et al. miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions. Gastroenterology. 2012;143(1):177–87. doi: 10.1053/j.gastro.2012.04.009. e178.PubMedCrossRefGoogle Scholar
  59. 59.
    Korkmaz G, le Sage C, Tekirdag KA, et al. miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1. Autophagy. 2012;8(2):165–76. doi: 10.4161/auto.8.2.18351.PubMedCrossRefGoogle Scholar
  60. 60.
    Zhai H, Fesler A, Ju J. MicroRNA: a third dimension in autophagy. Cell Cycle. 2013;12(2):246–50. doi: 10.4161/cc.23273.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Shen G, Li X, Jia YF, et al. Hypoxia-regulated microRNAs in human cancer. Acta Pharmacol Sin. 2013;34(3):336–41. doi: 10.1038/aps.2012.195.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Ma Y, Yang HZ, Dong BJ, et al. Biphasic regulation of autophagy by miR-96 in prostate cancer cells under hypoxia. Oncotarget. 2014;5(19):9169–82.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Ao JE, Kuang LH, Zhou Y, et al. Hypoxia-inducible factor 1 regulated ARC expression mediated hypoxia induced inactivation of the intrinsic death pathway in p53 deficient human colon cancer cells. Biochem Biophys Res Commun. 2012;420(4):913–7. doi: 10.1016/j.bbrc.2012.03.101.PubMedCrossRefGoogle Scholar
  64. 64.
    Li W, Zhang X, Zhuang H, et al. MicroRNA-137 is a novel hypoxia-responsive microRNA that inhibits mitophagy via regulation of two mitophagy receptors FUNDC1 and NIX. J Biol Chem. 2014;289(15):10691–701. doi: 10.1074/jbc.M113.537050.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Zhai H, Song B, Xu X, et al. Inhibition of autophagy and tumor growth in colon cancer by miR-502. Oncogene. 2013;32(12):1570–9. doi: 10.1038/onc.2012.167.PubMedCrossRefGoogle Scholar
  66. 66.
    Chen S, Li P, Li J, et al. MiR-144 inhibits proliferation and induces apoptosis and autophagy in lung cancer cells by targeting TIGAR. Cell Physiol Biochem. 2015;35(3):997–1007. doi: 10.1159/000369755.PubMedCrossRefGoogle Scholar
  67. 67.
    Spizzo R, Almeida MI, Colombatti A, Calin GA. Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene. 2012;31(43):4577–87. doi: 10.1038/onc.2011.621.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Prensner JR, Chinnaiyan AM. The emergence of lncRNAs in cancer biology. Can Dis. 2011;1(5):391–407. doi: 10.1158/2159-8290.CD-11-0209.CrossRefGoogle Scholar
  69. 69.
    St Laurent G, Wahlestedt C, Kapranov P. The landscape of long non-coding RNA classification. Trends Genet. 2015;31(5):239–51. doi: 10.1016/j.tig.2015.03.007.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Mitra SA, Mitra AP, Triche TJ. A central role for long non-coding RNA in cancer. Front Genet. 2012;3:17. doi: 10.3389/fgene.2012.00017.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Cheetham SW, Gruhl F, Mattick JS, Dinger ME. Long non-coding RNAs and the genetics of cancer. Br J Cancer. 2013;108(12):2419–25. doi: 10.1038/bjc.2013.233.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Nie FQ, Sun M, Yang JS, et al. Long non-coding RNA ANRIL promotes non-small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and P21 expression. Mol Cancer Ther. 2015;14(1):268–77. doi: 10.1158/1535-7163.MCT-14-0492.PubMedCrossRefGoogle Scholar
  73. 73.
    Yao Y, Ma J, Xue Y, et al. Knockdown of long non-coding RNA XIST exerts tumor-suppressive functions in human glioblastoma stem cells by up-regulating miR-152. Cancer Lett. 2015;359(1):75–86. doi: 10.1016/j.canlet.2014.12.051.PubMedCrossRefGoogle Scholar
  74. 74.
    Qiu JJ, Wang Y, Ding JX, et al. The long non-coding RNA HOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis. Exp Cell Res. 2015;333(2):238–48. doi: 10.1016/j.yexcr.2015.03.005.PubMedCrossRefGoogle Scholar
  75. 75.
    Wan J, Huang M, Zhao H, et al. A novel tetranucleotide repeat polymorphism within KCNQ1OT1 confers risk for hepatocellular carcinoma. DNA Cell Biol. 2013;32(11):628–34. doi: 10.1089/dna.2013.2118.PubMedCrossRefGoogle Scholar
  76. 76.
    Sun H, Wang G, Peng Y, et al. H19 lncRNA mediates 17beta-estradiol-induced cell proliferation in MCF-7 breast cancer cells. Oncol Rep. 2015;33:3045–52. doi: 10.3892/or.2015.3899.PubMedGoogle Scholar
  77. 77.
    Leygue E. Steroid receptor RNA activator (SRA1): unusual bifaceted gene products with suspected relevance to breast cancer. Nucl Recept Signal. 2007;5, e006. doi: 10.1621/nrs.05006.PubMedPubMedCentralGoogle Scholar
  78. 78.
    Hu L, Wu Y, Tan D, et al. Up-regulation of long non-coding RNA MALAT1 contributes to proliferation and metastasis in esophageal squamous cell carcinoma. J Exp Clin Cancer Res. 2015;34(1):7. doi: 10.1186/s13046-015-0123-z.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Wang X, Li M, Wang Z, et al. Silencing of long non-coding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration, and invasion of esophageal squamous cell carcinoma cells. J Biol Chem. 2015;290(7):3925–35. doi: 10.1074/jbc.M114.596866.PubMedCrossRefGoogle Scholar
  80. 80.
    Li J, Jiang K, Zhao F. Icariin regulates the proliferation and apoptosis of human ovarian cancer cells through microRNA-21 by targeting PTEN, RECK and Bcl-2. Oncol Rep. 2015;33:2829–36. doi: 10.3892/or.2015.3891.PubMedGoogle Scholar
  81. 81.
    Chen CL, Tseng YW, Wu JC, et al. Suppression of hepatocellular carcinoma by baculovirus-mediated expression of long non-coding RNA PTENP1 and MicroRNA regulation. Biomaterials. 2015;44:71–81. doi: 10.1016/j.biomaterials.2014.12.023.PubMedCrossRefGoogle Scholar
  82. 82.
    Wang Y, He L, Du Y, et al. The long non-coding RNA lncTCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling. Cell Stem Cell. 2015;16(4):413–25. doi: 10.1016/j.stem.2015.03.003.PubMedCrossRefGoogle Scholar
  83. 83.
    Jiao F, Hu H, Han T, et al. Long non-coding RNA MALAT-1 enhances stem cell-like phenotypes in pancreatic cancer cells. Int J Mol Sci. 2015;16(4):6677–93. doi: 10.3390/ijms16046677.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Williams GH, Stoeber K. The cell cycle and cancer. J Pathol. 2012;226(2):352–64. doi: 10.1002/path.3022.PubMedCrossRefGoogle Scholar
  85. 85.
    Casimiro MC, Crosariol M, Loro E, et al. Cyclins and cell cycle control in cancer and disease. Genes Cancer. 2012;3(11–12):649–57. doi: 10.1177/1947601913479022.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 2003;36(3):131–49.PubMedCrossRefGoogle Scholar
  87. 87.
    Kitagawa M, Kitagawa K, Kotake Y, et al. Cell cycle regulation by long non-coding RNAs. Cell Mol Life Sci. 2013;70(24):4785–94. doi: 10.1007/s00018-013-1423-0.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Leveille N, Melo CA, Rooijers K, et al. Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA. Nat Commun. 2015;6:6520. doi: 10.1038/ncomms7520.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Tripathi V, Shen Z, Chakraborty A, et al. Long non-coding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet. 2013;9(3):e1003368. doi: 10.1371/journal.pgen.1003368.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Kim T, Jeon YJ, Cui R, et al. Role of MYC-regulated long non-coding RNAs in cell cycle regulation and tumorigenesis. J Natl Cancer Inst. 2015;107(4):dju505.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Zhang Y, Ma M, Liu W, et al. Enhanced expression of long non-coding RNA CARLo-5 is associated with the development of gastric cancer. Int J Clin Exp Pathol. 2014;7(12):8471–9.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Shi Y, Liu Y, Wang J, et al. Down-regulated long non-coding RNA BANCR promotes the proliferation of colorectal cancer cells via downregulation of p21 expression. PLoS One. 2015;10(4):e0122679. doi: 10.1371/journal.pone.0122679.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Yang Q, Xu E, Dai J, et al. A novel long non-coding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015;285(2):79–88. doi: 10.1016/j.taap.2015.04.003.PubMedCrossRefGoogle Scholar
  94. 94.
    Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495–516. doi: 10.1080/01926230701320337.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Sanchez Y, Segura V, Marin-Bejar O, et al. Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature. Nat Commun. 2014;5:5812. doi: 10.1038/ncomms6812.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Yoon JH, Abdelmohsen K, Srikantan S, et al. LincRNA-p21 suppresses target mRNA translation. Mol Cell. 2012;47(4):648–55. doi: 10.1016/j.molcel.2012.06.027.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Luo H, Sun Y, Wei G, et al. Functional characterization of long non-coding RNA Lnc_bc060912 in human lung carcinoma cells. Biochemistry. 2015;54:2895–902. doi: 10.1021/acs.biochem.5b00259.PubMedCrossRefGoogle Scholar
  98. 98.
    Lu KH, Li W, Liu XH, et al. Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer. 2013;13:461. doi: 10.1186/1471-2407-13-461.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Han L, Zhang EB, Yin DD, et al. Low expression of long non-coding RNA PANDAR predicts a poor prognosis of non-small cell lung cancer and affects cell apoptosis by regulating Bcl-2. Cell Death Dis. 2015;6:e1665. doi: 10.1038/cddis.2015.30.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    DeOcesano-Pereira C, Amaral MS, Parreira KS, et al. Long non-coding RNA INXS is a critical mediator of BCL-XS induced apoptosis. Nucleic Acids Res. 2014;42(13):8343–55. doi: 10.1093/nar/gku561.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Pickard MR, Mourtada-Maarabouni M, Williams GT. Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines. Biochim Biophys Acta. 2013;1832(10):1613–23. doi: 10.1016/j.bbadis.2013.05.005.PubMedCrossRefGoogle Scholar
  102. 102.
    Hang Q, Sun R, Jiang C, Li Y. Notch 1 promotes cisplatin-resistant gastric cancer formation by up-regulating lncRNA AK022798 expression. Anticancer Drugs. 2015;26:632–40. doi: 10.1097/CAD.0000000000000227.PubMedGoogle Scholar
  103. 103.
    Zhao H, Zhang X, Frazao JB, et al. HOX antisense lincRNA HOXA-AS2 is an apoptosis repressor in all trans retinoic acid treated NB4 promyelocytic leukemia cells. J Cell Biochem. 2013;114(10):2375–83. doi: 10.1002/jcb.24586.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Liu Q, Sun S, Yu W, et al. Altered expression of long non-coding RNAs during genotoxic stress-induced cell death in human glioma cells. J Neurooncol. 2015;122(2):283–92. doi: 10.1007/s11060-015-1718-0.PubMedCrossRefGoogle Scholar
  105. 105.
    Kania E, Pajak B, Orzechowski A. Calcium homeostasis and ER stress in control of autophagy in cancer cells. Biomed Res Int. 2015;2015:352794. doi: 10.1155/2015/352794.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Lorin S, Hamai A, Mehrpour M, Codogno P. Autophagy regulation and its role in cancer. Semin Cancer Biol. 2013;23(5):361–79. doi: 10.1016/j.semcancer.2013.06.007.PubMedCrossRefGoogle Scholar
  107. 107.
    Wang K, Liu CY, Zhou LY, et al. APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p. Nat Commun. 2015;6:6779. doi: 10.1038/ncomms7779.PubMedCrossRefGoogle Scholar
  108. 108.
    Wang Y, Guo Q, Zhao Y, et al. BRAF-activated long non-coding RNA contributes to cell proliferation and activates autophagy in papillary thyroid carcinoma. Oncol Lett. 2014;8(5):1947–52. doi: 10.3892/ol.2014.2487.PubMedPubMedCentralGoogle Scholar
  109. 109.
    Ying L, Huang Y, Chen H, et al. Down-regulated MEG3 activates autophagy and increases cell proliferation in bladder cancer. Mol Biosyst. 2013;9(3):407–11. doi: 10.1039/c2mb25386k.PubMedCrossRefGoogle Scholar
  110. 110.
    Hayashi Y, Kuroda T, Kishimoto H, et al. Down-regulation of rRNA transcription triggers cell differentiation. PLoS One. 2014;9(5):e98586. doi: 10.1371/journal.pone.0098586.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Sharp SJ, Schaack J, Cooley L, et al. Structure and transcription of eukaryotic tRNA genes. CRC Crit Rev Biochem. 1985;19(2):107–44.PubMedCrossRefGoogle Scholar
  112. 112.
    Hadjiolov AA, Venkov PV, Tsanev RG. Ribonucleic acids fractionation by density-gradient centrifugation and by agar gel electrophoresis: a comparison. Anal Biochem. 1966;17(2):263–7.PubMedCrossRefGoogle Scholar
  113. 113.
    Dupuis-Sandoval F, Poirier M, Scott MS. The emerging landscape of small nucleolar RNAs in cell biology. Wiley Interdiscip Rev RNA. 2015;6:381–97. doi: 10.1002/wrna.1284.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Cheng J, Guo JM, Xiao BX, et al. piRNA, the new non-coding RNA, is aberrantly expressed in human cancer cells. Clin Chim Acta. 2011;412(17–18):1621–5. doi: 10.1016/j.cca.2011.05.015.PubMedCrossRefGoogle Scholar
  115. 115.
    Agrawal N, Dasaradhi PV, Mohmmed A, et al. RNA interference: biology, mechanism, and applications. Microbiol Mol Biol Rev. 2003;67(4):657–85.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Li P, Chen S, Chen H, et al. Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clin Chim Acta. 2015;444:132–6. doi: 10.1016/j.cca.2015.02.018.PubMedCrossRefGoogle Scholar
  117. 117.
    Chen LL, Yang L. Regulation of circRNA biogenesis. RNA Biol. 2015;12(4):381–8. doi: 10.1080/15476286.2015.1020271.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Zhang Q, Shalaby NA, Buszczak M. Changes in rRNA transcription influence proliferation and cell fate within a stem cell lineage. Science. 2014;343(6168):298–301. doi: 10.1126/science.1246384.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Maute RL, Schneider C, Sumazin P, et al. tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. Proc Natl Acad Sci U S A. 2013;110(4):1404–9. doi: 10.1073/pnas.1206761110.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Pacilli A, Ceccarelli C, Trere D, Montanaro L. SnoRNA U50 levels are regulated by cell proliferation and rRNA transcription. Int J Mol Sci. 2013;14(7):14923–35. doi: 10.3390/ijms140714923.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Bachmayr-Heyda A, Reiner AT, Auer K, et al. Correlation of circular RNA abundance with proliferation--exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues. Sci Rep. 2015;5:8057. doi: 10.1038/srep08057.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Cox DN, Chao A, Baker J, et al. A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes Dev. 1998;12(23):3715–27.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Wang Y, Jiang Y, Bian C, et al. Overexpression of Hiwi inhibits the cell growth of chronic myeloid leukemia K562 cells and enhances their chemosensitivity to daunomycin. Cell Biochem Biophys. 2015;73:129–35. doi: 10.1007/s12013-015-0668-7.PubMedCrossRefGoogle Scholar
  124. 124.
    Xie Y, Yang Y, Ji D, Zhang D, et al. Hiwi down-regulation, mediated by shRNA, reduces the proliferation and migration of human hepatocellular carcinoma cells. Mol Med Rep. 2015;11(2):1455–61. doi: 10.3892/mmr.2014.2847.PubMedGoogle Scholar
  125. 125.
    Wang Y, Jiang Y, Ma N, et al. Overexpression of Hiwi inhibits the growth and migration of chronic myeloid leukemia cells. Cell Biochem Biophys. 2015;73:117–24. doi: 10.1007/s12013-015-0651-3.PubMedCrossRefGoogle Scholar
  126. 126.
    Liang D, Dong M, Hu LJ, et al. Hiwi knockdown inhibits the growth of lung cancer in nude mice. Asian Pac J Cancer Prev. 2013;14(2):1067–72.PubMedCrossRefGoogle Scholar
  127. 127.
    Liang D, Fang Z, Dong M, et al. Effect of RNA interference-related HiWi gene expression on the proliferation and apoptosis of lung cancer stem cells. Oncol Lett. 2012;4(1):146–50. doi: 10.3892/ol.2012.677.PubMedPubMedCentralGoogle Scholar
  128. 128.
    He X, Qian Y, Cai H, Wang Z. The effect of RhoC siRNA on the invasiveness and proliferation of human cervical cancer cell line SiHa cells. J Huazhong Univ Sci Technolog Med Sci. 2008;28(6):665–9. doi: 10.1007/s11596-008-0611-x.PubMedCrossRefGoogle Scholar
  129. 129.
    Yang LJ, Chen Y, Ma Q, et al. Effect of betulinic acid on the regulation of Hiwi and cyclin B1 in human gastric adenocarcinoma AGS cells. Acta Pharmacol Sin. 2010;31(1):66–72. doi: 10.1038/aps.2009.177.PubMedCrossRefGoogle Scholar
  130. 130.
    Kato K, Hitomi Y, Imamura K, Esumi H. Hyperstable U1snRNA complementary to the K-ras transcripts induces cell death in pancreatic cancer cells. Br J Cancer. 2002;87(8):898–904. doi: 10.1038/sj.bjc.6600563.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT. GAS5, a non-protein-coding RNA, controls apoptosis and is down-regulated in breast cancer. Oncogene. 2009;28(2):195–208. doi: 10.1038/onc.2008.373.PubMedCrossRefGoogle Scholar
  132. 132.
    Wang X, Tong X, Gao H, et al. Silencing HIWI suppresses the growth, invasion and migration of glioma cells. Int J Oncol. 2014;45(6):2385–92. doi: 10.3892/ijo.2014.2673.PubMedGoogle Scholar
  133. 133.
    Hwang CJ, Fields JR, Shiao YH. Non-coding rRNA-mediated preferential killing in cancer cells is enhanced by suppression of autophagy in non-transformed counterpart. Cell Death Dis. 2011;2:e239. doi: 10.1038/cddis.2011.110.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Zaravinos A. The regulatory role of MicroRNAs in EMT and cancer. J Oncol. 2015;2015:865816. doi: 10.1155/2015/865816.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Suzuki R, Honda S, Kirino Y. PIWI expression and function in cancer. Front Genet. 2012;3:204. doi: 10.3389/fgene.2012.00204.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Singapore 2016

Authors and Affiliations

  1. 1.Second Military Medical UniversityShanghaiChina

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