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Unraveling the Complex Network of Interactions Between Noncoding RNAs and Epigenetics in Cancer

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Non-coding RNAs and Cancer

Abstract

Epigenetics is the study of heritable changes in gene expression that do not involve changes in the underlying DNA sequence. The most studied epigenetic modifications include DNA methylation and histone changes. These modifications are able to modulate the chromatin conformation and have a critical role in regulating gene expression. Over the last years, growing evidences have revealed the crucial role of epigenetic mechanisms controlling noncoding RNAs (ncRNAs) expression, in the same way as previously shown for protein-coding genes. Most interestingly, the link between ncRNAs and epigenetics is not limited to epigenetic regulation of ncRNAs, but also takes place in the opposite direction, meaning that these RNA molecules are able to control gene expression by regulating effectors of the epigenetic machinery. In this chapter both of these scenarios will be discussed, focusing in the cancer context. The complex network of reciprocal interactions between ncRNAs and epigenetics is just beginning to unravel and an exciting future in research about the role of ncRNAs in cancer epigenetics is guaranteed.

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References

  1. Waddington CH. Preliminary notes on the development of the wings in normal and mutant strains of Drosophila. Proc Natl Acad Sci U S A. 1939;25(7):299–307.

    Article  CAS  PubMed  Google Scholar 

  2. Holliday R. The inheritance of epigenetic defects. Science. 1987;238(4824):163–70.

    Article  CAS  PubMed  Google Scholar 

  3. Antequera F. Structure, function and evolution of CpG island promoters. Cell Mol Life Sci. 2003;60(8):1647–58.

    Article  CAS  PubMed  Google Scholar 

  4. Esteller M. Epigenetics in cancer. N Engl J Med. 2008;358(11):1148–59.

    Article  CAS  PubMed  Google Scholar 

  5. Esteller M. CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future. Oncogene. 2002;21(35):5427–40.

    Article  CAS  PubMed  Google Scholar 

  6. Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000; 403(6765):41–5.

    Article  CAS  PubMed  Google Scholar 

  7. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128(4):693–705.

    Article  CAS  PubMed  Google Scholar 

  8. Chi P, Allis CD, Wang GG. Covalent histone modifications–miswritten, misinterpreted and mis-erased in human cancers. Nat Rev Cancer. 2010;10(7):457–69.

    Article  CAS  PubMed  Google Scholar 

  9. Margueron R, Reinberg D. The polycomb complex PRC2 and its mark in life. Nature. 2011;469(7330):343–9.

    Article  CAS  PubMed  Google Scholar 

  10. Saito Y, Liang G, Egger G, et al. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell. 2006;9(6):435–43.

    Article  CAS  PubMed  Google Scholar 

  11. Scott GK, Mattie MD, Berger CE, et al. Rapid alteration of microRNA levels by histone deacetylase inhibition. Cancer Res. 2006;66(3):1277–81.

    Article  CAS  PubMed  Google Scholar 

  12. Lujambio A, Ropero S, Ballestar E, et al. Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res. 2007;67(4):1424–9.

    Article  CAS  PubMed  Google Scholar 

  13. Silber J, Lim DA, Petritsch C, et al. miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med 2008;6:14.

    Google Scholar 

  14. Ando T, Yoshida T, Enomoto S, et al. DNA methylation of microRNA genes in gastric mucosae of gastric cancer patients: its possible involvement in the formation of epigenetic field defect. Int J Cancer. 2009;124(10):2367–74.

    Article  CAS  PubMed  Google Scholar 

  15. Agirre X, Vilas-Zornoza A, Jimenez-Velasco A, et al. Epigenetic silencing of the tumor suppressor microRNA Hsa-miR-124a regulates CDK6 expression and confers a poor prognosis in acute lymphoblastic leukemia. Cancer Res. 2009;69(10):4443–53.

    Article  CAS  PubMed  Google Scholar 

  16. Roman-Gomez J, Agirre X, Jimenez-Velasco A, et al. Epigenetic regulation of microRNAs in acute lymphoblastic leukemia. J Clin Oncol. 2009;27(8):1316–22.

    Article  CAS  PubMed  Google Scholar 

  17. Furuta M, Kozaki KI, Tanaka S, et al. miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis. 2010;31(5): 766–76.

    Article  CAS  PubMed  Google Scholar 

  18. Wilting SM, van Boerdonk RA, Henken FE, et al. Methylation-mediated silencing and tumour suppressive function of hsa-miR-124 in cervical cancer. Mol Cancer. 2010;9167.

    Google Scholar 

  19. Brueckner B, Stresemann C, Kuner R, et al. The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function. Cancer Res. 2007;67(4):1419–23.

    Article  CAS  PubMed  Google Scholar 

  20. Lu L, Katsaros D, de la Longrais IA, et al. Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-II expression and favorable prognosis. Cancer Res. 2007;67(21):10117–22.

    Article  CAS  PubMed  Google Scholar 

  21. Lu L, Katsaros D, Zhu Y, et al. Let-7a regulation of insulin-like growth factors in breast cancer. Breast Cancer Res Treat. 2011;126(3):687–94.

    Article  CAS  PubMed  Google Scholar 

  22. Datta J, Kutay H, Nasser MW, et al. Methylation mediated silencing of MicroRNA-1 gene and its role in hepatocellular carcinogenesis. Cancer Res. 2008;68(13):5049–58.

    Article  CAS  PubMed  Google Scholar 

  23. Lehmann U, Hasemeier B, Christgen M, et al. Epigenetic inactivation of microRNA gene hsa-mir-9-1 in human breast cancer. J Pathol. 2008;214(1):17–24.

    Article  CAS  PubMed  Google Scholar 

  24. Lujambio A, Calin GA, Villanueva A, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci U S A. 2008;105(36):13556–61.

    Article  CAS  PubMed  Google Scholar 

  25. Bandres E, Agirre X, Bitarte N, et al. Epigenetic regulation of microRNA expression in colorectal cancer. Int J Cancer. 2009;125(11):2737–43.

    Article  CAS  PubMed  Google Scholar 

  26. Hildebrandt MA, Gu J, Lin J, et al. Hsa-miR-9 methylation status is associated with cancer development and metastatic recurrence in patients with clear cell renal cell carcinoma. Oncogene. 2010;29(42):5724–8.

    Article  CAS  PubMed  Google Scholar 

  27. Heller G, Weinzierl M, Noll C, et al. Genome-wide miRNA expression profiling identifies miR-9-3 and miR-193a as targets for DNA methylation in Non-small cell lung cancers. Clin Cancer Res. 2012;18(6):1619–29.

    Article  CAS  PubMed  Google Scholar 

  28. Sampath D, Liu C, Vasan K, et al. Histone deacetylases mediate the silencing of miR-15a, miR-16, and miR-29b in chronic lymphocytic leukemia. Blood. 2012;119(5):1162–72.

    Article  CAS  PubMed  Google Scholar 

  29. Humphreys KJ, Cobiac L, Le Leu RK, et al. Histone deacetylase inhibition in colorectal cancer cells reveals competing roles for members of the oncogenic miR-17-92 cluster. Mol Carcinog. 2013;52(6):459–74. doi:10.1002/mc.21879.

    Google Scholar 

  30. Augoff K, Mccue B, Plow EF, et al. miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer. Mol Cancer 2012;11:5.

    Google Scholar 

  31. Toyota M, Suzuki H, Sasaki Y, et al. Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res. 2008;68(11):4123–32.

    Article  CAS  PubMed  Google Scholar 

  32. Chim CS, Wan TS, Wong KY, et al. Methylation of miR-34a, miR-34b/c, miR-124-1 and miR-203 in Ph-negative myeloproliferative neoplasms. J Transl Med. 2011;9:197.

    Article  PubMed  CAS  Google Scholar 

  33. Tsai KW, Wu CW, Hu LY, et al. Epigenetic regulation of miR-34b and miR-129 expression in gastric cancer. Int J Cancer. 2011;129(11):2600–10.

    Article  CAS  PubMed  Google Scholar 

  34. Lee KH, Lotterman C, Karikari C, et al. Epigenetic silencing of MicroRNA miR-107 regulates cyclin-dependent kinase 6 expression in pancreatic cancer. Pancreatology. 2009;9(3):293–301.

    Article  CAS  PubMed  Google Scholar 

  35. Huang YW, Liu JC, Deatherage DE, et al. Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 oncogene in endometrial cancer. Cancer Res. 2009;69(23):9038–46.

    Article  CAS  PubMed  Google Scholar 

  36. Shen R, Pan S, Qi S, et al. Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 in gastric cancer. Biochem Biophys Res Commun. 2010;394(4):1047–52.

    Article  CAS  PubMed  Google Scholar 

  37. Balaguer F, Link A, Lozano JJ, et al. Epigenetic silencing of miR-137 is an early event in colorectal carcinogenesis. Cancer Res. 2010;70(16):6609–18.

    Article  CAS  PubMed  Google Scholar 

  38. Langevin SM, Stone RA, Bunker CH, et al. MicroRNA-137 promoter methylation in oral rinses from patients with squamous cell carcinoma of the head and neck is associated with gender and body mass index. Carcinogenesis. 2010;31(5):864–70.

    Article  CAS  PubMed  Google Scholar 

  39. Chen Q, Chen X, Zhang M, et al. miR-137 is frequently down-regulated in gastric cancer and is a negative regulator of Cdc42. Dig Dis Sci. 2011;56(7):2009–16.

    Article  CAS  PubMed  Google Scholar 

  40. Chen Y, Luo J, Tian R, et al. miR-373 negatively regulates methyl-CpG-binding domain protein 2 (MBD2) in hilar cholangiocarcinoma. Dig Dis Sci. 2011;56(6):1693–701.

    Article  CAS  PubMed  Google Scholar 

  41. Langevin SM, Stone RA, Bunker CH, et al. MicroRNA-137 promoter methylation is associated with poorer overall survival in patients with squamous cell carcinoma of the head and neck. Cancer. 2011;117(7):1454–62.

    Article  CAS  PubMed  Google Scholar 

  42. Wiklund ED, Gao S, Hulf T, et al. MicroRNA alterations and associated aberrant DNA methylation patterns across multiple sample types in oral squamous cell carcinoma. PLoS One. 2011;6(11):e27840.

    Article  CAS  PubMed  Google Scholar 

  43. Kozaki K, Imoto I, Mogi S, et al. Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Res. 2008;68(7):2094–105.

    Article  CAS  PubMed  Google Scholar 

  44. Gao XN, Lin J, Li YH, et al. MicroRNA-193a represses c-kit expression and functions as a methylation-silenced tumor suppressor in acute myeloid leukemia. Oncogene. 2011;30(31): 3416–28.

    Article  CAS  PubMed  Google Scholar 

  45. Schotte D, Lange-Turenhout EA, Stumpel DJ, et al. Expression of miR-196b is not exclusively MLL-driven but is especially linked to activation of HOXA genes in pediatric acute lymphoblastic leukemia. Haematologica. 2010;95(10):1675–82.

    Article  CAS  PubMed  Google Scholar 

  46. Tsai KW, Hu LY, Wu CW, et al. Epigenetic regulation of miR-196b expression in gastric cancer. Genes Chromosomes Cancer. 2010;49(11):969–80.

    Article  CAS  PubMed  Google Scholar 

  47. Ueda T, Volinia S, Okumura H, et al. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 2010; 11(2):136–46.

    Article  CAS  PubMed  Google Scholar 

  48. Yin G, Chen R, Alvero AB, et al. TWISTing stemness, inflammation and proliferation of epithelial ovarian cancer cells through MIR199A2/214. Oncogene. 2010;29(24):3545–53.

    Article  CAS  PubMed  Google Scholar 

  49. Cheung HH, Davis AJ, Lee TL, et al. Methylation of an intronic region regulates miR-199a in testicular tumor malignancy. Oncogene. 2011;30(31):3404–15.

    Article  CAS  PubMed  Google Scholar 

  50. Ceppi P, Mudduluru G, Kumarswamy R, et al. Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer. Mol Cancer Res. 2010;8(9):1207–16.

    Article  CAS  PubMed  Google Scholar 

  51. Neves R, Scheel C, Weinhold S, et al. Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast cancer cells. BMC Res Notes. 2010;3:219.

    Article  PubMed  CAS  Google Scholar 

  52. Vrba L, Jensen TJ, Garbe JC, et al. Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells. PLoS One. 2010;5(1):e8697.

    Article  PubMed  CAS  Google Scholar 

  53. Davalos V, Moutinho C, Villanueva A, et al. Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis. Oncogene. 2011;31(16):2062–74.

    Article  PubMed  CAS  Google Scholar 

  54. Wiklund ED, Bramsen JB, Hulf T, et al. Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer. Int J Cancer. 2011;128(6):1327–34.

    Article  CAS  PubMed  Google Scholar 

  55. Craig VJ, Cogliatti SB, Rehrauer H, et al. Epigenetic silencing of microRNA-203 dysregulates ABL1 expression and drives Helicobacter-associated gastric lymphomagenesis. Cancer Res. 2011;71(10):3616–24.

    Article  CAS  PubMed  Google Scholar 

  56. Chim CS, Wong KY, Leung CY, et al. Epigenetic inactivation of the hsa-miR-203 in haematological malignancies. J Cell Mol Med. 2011;15(12):2760–7.

    Article  CAS  PubMed  Google Scholar 

  57. Tellez CS, Juri DE, Do K, et al. EMT and stem cell-like properties associated with miR-205 and miR-200 epigenetic silencing are early manifestations during carcinogen-induced transformation of human lung epithelial cells. Cancer Res. 2011;71(8):3087–97.

    Article  CAS  PubMed  Google Scholar 

  58. Wang Y, Toh HC, Chow P, et al. MicroRNA-224 is up-regulated in hepatocellular carcinoma through epigenetic mechanisms. FASEB J. 2012;26(7):3032–41. doi:10.1096/fj.11-201855.

    Google Scholar 

  59. Ferreira HJ, Heyn H, Moutinho C, et al. CpG island hypermethylation-associated silencing of small nucleolar RNAs in human cancer. RNA Biol. 2012;9(6):881–90.

    Article  CAS  PubMed  Google Scholar 

  60. Cheung HH, Lee TL, Davis AJ, et al. Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer. Br J Cancer. 2010;102(2):419–27.

    Article  CAS  PubMed  Google Scholar 

  61. Lujambio A, Portela A, Liz J, et al. CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer. Oncogene. 2010;29(48):6390–401.

    Article  CAS  PubMed  Google Scholar 

  62. Zhao J, Dahle D, Zhou Y, et al. Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors. J Clin Endocrinol Metab. 2005; 90(4):2179–86.

    Article  CAS  PubMed  Google Scholar 

  63. Benetatos L, Dasoula A, Hatzimichael E, et al. Promoter hypermethylation of the MEG3 (DLK1/MEG3) imprinted gene in multiple myeloma. Clin Lymphoma Myeloma. 2008;8(3):171–5.

    Article  CAS  PubMed  Google Scholar 

  64. Gejman R, Batista DL, Zhong Y, et al. Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas. J Clin Endocrinol Metab. 2008;93(10): 4119–25.

    Article  CAS  PubMed  Google Scholar 

  65. Benetatos L, Hatzimichael E, Dasoula A, et al. CpG methylation analysis of the MEG3 and SNRPN imprinted genes in acute myeloid leukemia and myelodysplastic syndromes. Leuk Res. 2010;34(2):148–53.

    Article  CAS  PubMed  Google Scholar 

  66. Calin GA, Dumitru CD, Shimizu M, et al. 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. 2002;99(24):15524–9.

    Article  CAS  PubMed  Google Scholar 

  67. Suzuki H, Takatsuka S, Akashi H, et al. Genome-wide profiling of chromatin signatures reveals epigenetic regulation of MicroRNA genes in colorectal cancer. Cancer Res. 2011; 71(17):5646–58.

    Article  CAS  PubMed  Google Scholar 

  68. Gerbi SA. Small nucleolar RNA. Biochem Cell Biol. 1995;73(11–12):845–58.

    Article  CAS  PubMed  Google Scholar 

  69. Kiss-Laszlo Z, Henry Y, Bachellerie JP, et al. Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs. Cell. 1996;85(7):1077–88.

    Article  CAS  PubMed  Google Scholar 

  70. Ganot P, Bortolin ML, Kiss T. Site-specific pseudouridine formation in preribosomal RNA is guided by small nucleolar RNAs. Cell. 1997;89(5):799–809.

    Article  CAS  PubMed  Google Scholar 

  71. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12(12):861–74.

    Article  CAS  PubMed  Google Scholar 

  72. Calin GA, Liu CG, Ferracin M, et al. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell. 2007;12(3):215–29.

    Article  CAS  PubMed  Google Scholar 

  73. Scaruffi P, Stigliani S, Moretti S, et al. Transcribed-ultra conserved region expression is associated with outcome in high-risk neuroblastoma. BMC Cancer. 2009;9:441.

    Article  PubMed  CAS  Google Scholar 

  74. Zhang X, Zhou Y, Mehta KR, et al. A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells. J Clin Endocrinol Metab. 2003;88(11):5119–26.

    Article  CAS  PubMed  Google Scholar 

  75. Guttman M, Amit I, Garber M, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–7.

    Article  CAS  PubMed  Google Scholar 

  76. Khalil AM, Guttman M, Huarte M, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009;106(28):11667–72.

    Article  CAS  PubMed  Google Scholar 

  77. Wu SC, Kallin EM, Zhang Y. Role of H3K27 methylation in the regulation of lncRNA expression. Cell Res. 2010;20(10):1109–16.

    Article  CAS  PubMed  Google Scholar 

  78. Fabbri M, Garzon R, Cimmino A, et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A. 2007;104(40):15805–10.

    Article  CAS  PubMed  Google Scholar 

  79. Garzon R, Liu S, Fabbri M, et al. MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood. 2009;113(25):6411–8.

    Article  CAS  PubMed  Google Scholar 

  80. Varambally S, Cao Q, Mani RS, et al. Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science. 2008;322(5908):1695–9.

    Article  CAS  PubMed  Google Scholar 

  81. Friedman JM, Liang G, Liu CC, et al. The putative tumor suppressor microRNA-101 modulates the cancer epigenome by repressing the polycomb group protein EZH2. Cancer Res. 2009;69(6):2623–9.

    Article  CAS  PubMed  Google Scholar 

  82. Song B, Wang Y, Xi Y, et al. Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells. Oncogene. 2009;28(46):4065–74.

    Article  CAS  PubMed  Google Scholar 

  83. Ng EK, Tsang WP, Ng SS, et al. MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer. Br J Cancer. 2009;101(4):699–706.

    Article  CAS  PubMed  Google Scholar 

  84. Duursma AM, Kedde M, Schrier M, et al. miR-148 targets human DNMT3b protein coding region. RNA. 2008;14(5):872–7.

    Article  CAS  PubMed  Google Scholar 

  85. Braconi C, Huang N, Patel T. MicroRNA-dependent regulation of DNA methyltransferase-1 and tumor suppressor gene expression by interleukin-6 in human malignant cholangiocytes. Hepatology. 2010;51(3):881–90.

    CAS  PubMed  Google Scholar 

  86. Zhang Z, Tang H, Wang Z, et al. MiR-185 targets the DNA methyltransferases 1 and regulates global DNA methylation in human glioma. Mol Cancer. 2011;10:124.

    Article  CAS  PubMed  Google Scholar 

  87. Wada R, Akiyama Y, Hashimoto Y, et al. miR-212 is downregulated and suppresses methyl-CpG-binding protein MeCP2 in human gastric cancer. Int J Cancer. 2010;127(5):1106–14.

    Article  CAS  PubMed  Google Scholar 

  88. Wang H, Wu J, Meng X, et al. MicroRNA-342 inhibits colorectal cancer cell proliferation and invasion by directly targeting DNA methyltransferase 1. Carcinogenesis. 2011;32(7): 1033–42.

    Article  CAS  PubMed  Google Scholar 

  89. Noonan EJ, Place RF, Pookot D, et al. miR-449a targets HDAC-1 and induces growth arrest in prostate cancer. Oncogene. 2009;28(14):1714–24.

    Article  CAS  PubMed  Google Scholar 

  90. Tsai MC, Manor O, Wan Y, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010;329(5992):689–93.

    Article  CAS  PubMed  Google Scholar 

  91. Gupta RA, Shah N, Wang KC, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6.

    Article  CAS  PubMed  Google Scholar 

  92. Kogo R, Shimamura T, Mimori K, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011;71(20):6320–6.

    Article  CAS  PubMed  Google Scholar 

  93. Niinuma T, Suzuki H, Nojima M, et al. Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. Cancer Res. 2012;72(5):1126–36.

    Article  CAS  PubMed  Google Scholar 

  94. Geng YJ, Xie SL, Li Q, et al. Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res. 2011;39(6):2119–28.

    Article  CAS  PubMed  Google Scholar 

  95. Yang Z, Zhou L, Wu LM, et al. Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol. 2011;18(5):1243–50.

    Article  PubMed  Google Scholar 

  96. Yu W, Gius D, Onyango P, et al. Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature. 2008;451(7175):202–6.

    Article  CAS  PubMed  Google Scholar 

  97. Yap KL, Li S, Munoz-Cabello AM, et al. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell. 2010;38(5):662–74.

    Article  CAS  PubMed  Google Scholar 

  98. Kotake Y, Nakagawa T, Kitagawa K, et al. Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene. 2011;30(16):1956–62.

    Article  CAS  PubMed  Google Scholar 

  99. Morris KV, Santoso S, Turner AM, et al. Bidirectional transcription directs both transcriptional gene activation and suppression in human cells. PLoS Genet. 2008;4(11):e1000258.

    Article  PubMed  CAS  Google Scholar 

  100. Huarte M, Guttman M, Feldser D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010;142(3):409–19.

    Article  CAS  PubMed  Google Scholar 

  101. Yang F, Zhang L, Huo XS, et al. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology. 2011;54(5):1679–89.

    Article  CAS  PubMed  Google Scholar 

  102. Wang X, Arai S, Song X, et al. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature. 2008;454(7200):126–30.

    Article  CAS  PubMed  Google Scholar 

  103. Watanabe T, Tomizawa S, Mitsuya K, et al. Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science. 2011;332(6031): 848–52.

    Article  CAS  PubMed  Google Scholar 

  104. Aravin AA, Sachidanandam R, Bourc’his D, et al. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell. 2008;31(6):785–99.

    Article  CAS  PubMed  Google Scholar 

  105. Kuramochi-Miyagawa S, Watanabe T, Gotoh K, et al. DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev. 2008;22(7):908–17.

    Article  CAS  PubMed  Google Scholar 

  106. Lee JH, Schutte D, Wulf G, et al. Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-XL pathway. Hum Mol Genet. 2006; 15(2):201–11.

    Article  CAS  PubMed  Google Scholar 

  107. 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.

    Article  CAS  PubMed  Google Scholar 

  108. Taubert H, Greither T, Kaushal D, et al. Expression of the stem cell self-renewal gene Hiwi and risk of tumour-related death in patients with soft-tissue sarcoma. Oncogene. 2007;26(7):1098–100.

    Article  CAS  PubMed  Google Scholar 

  109. 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.

    PubMed  Google Scholar 

  110. 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.

    Article  CAS  PubMed  Google Scholar 

  111. Cheng J, Deng H, Xiao B, et al. piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells. Cancer Lett. 2012;315(1):12–7.

    Article  CAS  PubMed  Google Scholar 

  112. Schmitz KM, Mayer C, Postepska A, et al. Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes. Genes Dev. 2010;24(20):2264–9.

    Article  CAS  PubMed  Google Scholar 

  113. Guttman M, Rinn JL. Modular regulatory principles of large non-coding RNAs. Nature. 2012;482(7385):339–46.

    Article  CAS  PubMed  Google Scholar 

  114. Penny GD, Kay GF, Sheardown SA, et al. Requirement for Xist in X chromosome inactivation. Nature. 1996;379(6561):131–7.

    Article  CAS  PubMed  Google Scholar 

  115. Zhao J, Sun BK, Erwin JA, et al. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science. 2008;322(5902):750–6.

    Article  CAS  PubMed  Google Scholar 

  116. Lee JT, Davidow LS, Warshawsky D. Tsix, a gene antisense to Xist at the X-inactivation centre. Nat Genet. 1999;21(4):400–4.

    Article  CAS  PubMed  Google Scholar 

  117. Ohhata T, Hoki Y, Sasaki H, et al. Crucial role of antisense transcription across the Xist promoter in Tsix-mediated Xist chromatin modification. Development. 2008;135(2):227–35.

    Article  CAS  PubMed  Google Scholar 

  118. Huang KC, Rao PH, Lau CC, et al. Relationship of XIST expression and responses of ovarian cancer to chemotherapy. Mol Cancer Ther. 2002;1(10):769–76.

    CAS  PubMed  Google Scholar 

  119. Sirchia SM, Tabano S, Monti L, et al. Misbehaviour of XIST RNA in breast cancer cells. PLoS One. 2009;4(5):e5559.

    Article  PubMed  CAS  Google Scholar 

  120. Weakley SM, Wang H, Yao Q, et al. Expression and function of a large non-coding RNA gene XIST in human cancer. World J Surg. 2012;35(8):1751–6.

    Article  Google Scholar 

  121. Agrelo R, Souabni A, Novatchkova M, et al. SATB1 defines the developmental context for gene silencing by Xist in lymphoma and embryonic cells. Dev Cell. 2009;16(4):507–16.

    Article  CAS  PubMed  Google Scholar 

  122. Han HJ, Russo J, Kohwi Y, et al. SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature. 2008;452(7184):187–93.

    Article  CAS  PubMed  Google Scholar 

  123. Sleutels F, Zwart R, Barlow DP. The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature. 2002;415(6873):810–3.

    Article  CAS  PubMed  Google Scholar 

  124. Yotova IY, Vlatkovic IM, Pauler FM, et al. Identification of the human homolog of the imprinted mouse Air non-coding RNA. Genomics. 2008;92(6):464–73.

    Article  CAS  PubMed  Google Scholar 

  125. Pandey RR, Mondal T, Mohammad F, et al. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell. 2008; 32(2):232–46.

    Article  CAS  PubMed  Google Scholar 

  126. Nakano S, Murakami K, Meguro M, et al. Expression profile of LIT1/KCNQ1OT1 and epigenetic status at the KvDMR1 in colorectal cancers. Cancer Sci. 2006;97(11):1147–54.

    Article  CAS  PubMed  Google Scholar 

  127. Hock H. A complex Polycomb issue: the two faces of EZH2 in cancer. Genes Dev. 2012; 26(8):751–5.

    Article  CAS  PubMed  Google Scholar 

  128. Simon C, Chagraoui J, Krosl J, et al. A key role for EZH2 and associated genes in mouse and human adult T-cell acute leukemia. Genes Dev. 2012;26(7):651–6.

    Article  CAS  PubMed  Google Scholar 

  129. Ntziachristos P, Tsirigos A, Van Vlierberghe P, et al. Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia. Nat Med. 2012;18(2):298–301.

    Article  CAS  PubMed  Google Scholar 

  130. Tong ZT, Cai MY, Wang XG, et al. EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin. Oncogene. 2012;31(5):583–94.

    CAS  PubMed  Google Scholar 

  131. Rinn JL, Kertesz M, Wang JK, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 2007;129(7):1311–23.

    Article  CAS  PubMed  Google Scholar 

  132. Pasmant E, Sabbagh A, Masliah-Planchon J, et al. Role of noncoding RNA ANRIL in genesis of plexiform neurofibromas in neurofibromatosis type 1. J Natl Cancer Inst. 2011;103(22): 1713–22.

    Article  CAS  PubMed  Google Scholar 

  133. Kim K, Choi J, Heo K, et al. Isolation and characterization of a novel H1.2 complex that acts as a repressor of p53-mediated transcription. J Biol Chem. 2008;283(14):9113–26.

    Article  CAS  PubMed  Google Scholar 

  134. Diehl JA. Cycling to cancer with cyclin D1. Cancer Biol Ther. 2002;1(3):226–31.

    CAS  PubMed  Google Scholar 

  135. Martianov I, Ramadass A, Serra Barros A, et al. Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript. Nature. 2007;445(7128):666–70.

    Article  CAS  PubMed  Google Scholar 

  136. McGuire JJ. Anticancer antifolates: current status and future directions. Curr Pharm Des. 2003;9(31):2593–613.

    Article  CAS  PubMed  Google Scholar 

  137. Kino T, Hurt DE, Ichijo T, et al. Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci Signal. 2010;3(107):ra8.

    Article  PubMed  CAS  Google Scholar 

  138. Mourtada-Maarabouni M, Pickard MR, Hedge VL, et al. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene. 2009;28(2):195–208.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

 V.D. is supported by Instituto de Salud Carlos III, Sara Borrell postdoctoral contract. M.E. is an Institucio Catalana de Recerca i Estudis Avançats (ICREA) Research Professor.

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Authors and Affiliations

  1. Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Hospital Duran i Reynals, L’Hospitalet, 3rd Floor, Av. Gran Via 199-203, 08907, Barcelona, Catalonia, Spain

    Veronica Davalos & Manel Esteller

  2. Departament de Ciencies Fisiologiques II, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain

    Manel Esteller

  3. Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain

    Manel Esteller

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  1. Veronica Davalos
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  2. Manel Esteller
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Correspondence to Manel Esteller .

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  1. Pediatrics and Molecular Microbiology &, University of Southern California Children's Hospital Los Angeles, Los Angeles, California, USA

    Muller Fabbri

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Davalos, V., Esteller, M. (2014). Unraveling the Complex Network of Interactions Between Noncoding RNAs and Epigenetics in Cancer. In: Fabbri, M. (eds) Non-coding RNAs and Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8444-8_7

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