Advertisement

MicroRNA Methylation in Colorectal Cancer

  • Sippy KaurEmail author
  • Johanna E. Lotsari-Salomaa
  • Riitta Seppänen-Kaijansinkko
  • Päivi Peltomäki
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 937)

Abstract

Epigenetic alterations such as DNA methylation, histone modifications and non-coding RNA (including microRNA) associated gene silencing have been identified as a major characteristic in human cancers. These alterations may occur more frequently than genetic mutations and play a key role in silencing tumor suppressor genes or activating oncogenes, thereby affecting multiple cellular processes. In recent years, studies have shown that microRNAs, that act as posttranscriptional regulators of gene expression are frequently deregulated in colorectal cancer (CRC), via aberrant DNA methylation. Over the past decade, technological advances have revolutionized the field of epigenetics and have led to the identification of numerous epigenetically dysregulated miRNAs in CRC, which are regulated by CpG island hypermethylation and DNA hypomethylation. In addition, aberrant DNA methylation of miRNA genes holds a great promise in several clinical applications such as biomarkers for early screening, prognosis, and therapeutic applications in CRC.

Keywords

MicroRNA Epigenetic regulation DNA methylation Colorectal cancer 

References

  1. 1.
    Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010;31:27–36.PubMedCrossRefGoogle Scholar
  2. 2.
    Medvedeva YA, Fridman MV, Oparina NJ. Intergenic, gene terminal, and intragenic CpG islands in the human genome. BMC Genomics. 2010;11.Google Scholar
  3. 3.
    Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16:6–21.PubMedCrossRefGoogle Scholar
  4. 4.
    Li W, Chen BF. Aberrant DNA methylation in human cancers. J Huazhong Univ Sci Technolog. 2013;33:798–804.CrossRefGoogle Scholar
  5. 5.
    Feinberg AP, Ohlsson R, Henikoff S. The epigenetic progenitor origin of human cancer. Nature Rev Genet. 2006;7:21–33.PubMedCrossRefGoogle Scholar
  6. 6.
    Migliore L, Migheli F, Spisni R, Coppede F. Genetics, cytogenetics, and epigenetics of colorectal cancer. J Biomed Biotechnol. 2011;2011:1–19.CrossRefGoogle Scholar
  7. 7.
    Pino MS, Chung DC. The chromosomal instability pathway in colon cancer. Gastroenterology. 2010;138:2059–72.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A. 1999;96:8681–6.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Issa JP. Colon cancer: it’s CIN or CIMP. Clin Cancer Res. 2009;19:5939–40.Google Scholar
  10. 10.
    Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006;38:787–93.PubMedCrossRefGoogle Scholar
  11. 11.
    Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology. 2007;50:113–30.PubMedCrossRefGoogle Scholar
  12. 12.
    de la Chapelle A. Microsatellite instability. N Eng J Med. 2003;349:209–10.CrossRefGoogle Scholar
  13. 13.
    Fearon ER. Molecular genetics of colorectal cancer. Annu Rev Pathol: Mech Dis. 2011;6:479–507. doi: 10.1146/annurev-pathol-011110-130235.CrossRefGoogle Scholar
  14. 14.
    Valeri N, Gasparini P, Fabbri M. Modulation of mismatch repair and genomic stability by miR-155. Proc Natl Acad Sci U S A. 2010;15:6982–7.CrossRefGoogle Scholar
  15. 15.
    El-Murr N, Abidi Z, Wanherdrick K, Svrcek M, Gaub MP, Flejou JF, et al. MiRNA genes constitute new targets for microsatellite instability in colorectal cancer. PLoS One. 2012;2:e31862.CrossRefGoogle Scholar
  16. 16.
    Balaguer F, Moreira L, Lozano JJ, Link A, Ramirez G, Shen Y, et al. Colorectal cancers with microsatellite instability display unique miRNA profiles. Clin Cancer Res. 2011;17:6239–49.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Sarver AL, French AJ, Borralho PM. Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states. BMC Cancer. 2009;9:401.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Ogino S, Goel A. Molecular classification and correlates in colorectal cancer. J Mol Diagn. 2008;1:13–27.CrossRefGoogle Scholar
  19. 19.
    Pavicic W, Perkio E, Kaur S, Peltomaki P. Altered methylation at microRNA-associated CpG islands in hereditary and sporadic carcinomas: a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA)-based approach. Mol Med. 2011;17:726–35.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Mei Q, Xue G, Li X, Wu Z, Li X, Yan H, et al. Methylation-induced loss of miR-484 in microsatellite-unstable colorectal cancer promotes both viability and IL-8 production via CD137L. J Pathol. 2015;236:165–74.PubMedCrossRefGoogle Scholar
  21. 21.
    He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522–31.PubMedCrossRefGoogle Scholar
  22. 22.
    Suzuki H, Maruyama R, Yamamoto E, Kai M. Epigenetic alteration and microRNA dysregulation in cancer. Front Genet. 2013;4:258.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Li Z, Rana TM. Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Dis. 2014;13:622–38.CrossRefGoogle Scholar
  24. 24.
    Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.PubMedCrossRefGoogle Scholar
  25. 25.
    Chan SP, Slack FJ. And now introducing mammalian mirtrons. Dev Cell. 2007;5:605–7.CrossRefGoogle Scholar
  26. 26.
    Saito Y, Jones PA. Epigenetic activation of tumor suppressor microRNAs in human cancer cells. Cell Cycle. 2006;5:2220–2.PubMedCrossRefGoogle Scholar
  27. 27.
    Weber B, Stresemann C, Brueckner B, Lyko F. Methylation of human microRNA genes in normal and neoplastic cells. Cell Cycle. 2007;6:1001–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Chien CH, Sun YM, Chang WC, Chiang Hsieh PY, Lee TY, Tsai WC, et al. Identifying transcriptional start sites of human microRNAs based on high-throughput sequencing data. Nucleic Acids Res. 2011;39:9345–56.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Ozsolak F, Poling LL, Wang Z, Liu H, Liu XS, Roeder RG, et al. Chromatin structure analyses identify miRNA promoters. Genes Dev. 2008;22:3172–83.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Suzuki H, Takatsuka S, Akashi H, Yamamoto E, Nojima M, Maruyama R, et al. Genome-wide profiling of chromatin signatures reveals epigenetic regulation of MicroRNA genes in colorectal cancer. Cancer Res. 2011;71:5646–58.PubMedCrossRefGoogle Scholar
  31. 31.
    Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P, et al. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet. 2009;41:178–86.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Dudziec E, Miah S, Choudhry HM, Owen HC, Blizard S, Glover M, et al. Hypermethylation of CpG islands and shores around specific microRNAs and mirtrons is associated with the phenotype and presence of bladder cancer. Clin Cancer Res. 2011;17:1287–96.PubMedCrossRefGoogle Scholar
  33. 33.
    Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, 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;104:15805–10.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Majid S, Dar AA, Saini S, Shahryari V, Arora S, Zaman MS, et al. miRNA-34b inhibits prostate cancer through demethylation, active chromatin modifications, and AKT pathways. Clin Cancer Res. 2013;1:73–84.CrossRefGoogle Scholar
  35. 35.
    Pavicic W, Joensuu EI, Nieminen T, Peltomaki P. LINE-1 hypomethylation in familial and sporadic cancer. J Mol Med (Berl). 2012;90:827–35.CrossRefGoogle Scholar
  36. 36.
    Brueckner B, Stresemann C, Kuner R, Mund C, Musch T, Meister M, et al. The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function. Cancer Res. 2007;67:1419–23.PubMedCrossRefGoogle Scholar
  37. 37.
    Baer C, Claus R, Frenzel LP, Zucknick M, Park YJ, Gu L, et al. Extensive promoter DNA hypermethylation and hypomethylation is associated with aberrant microRNA expression in chronic lymphocytic leukemia. Cancer Res. 2012;72:3775–85.PubMedCrossRefGoogle Scholar
  38. 38.
    He XX, Kuang SZ, Liao JZ, Xu CR, Chang Y, Wu YL, et al. The regulation of microRNA expression by DNA methylation in hepatocellular carcinoma. Mol Biosyst. 2015;11:532–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Lao VV, Grady WM. Epigenetics and colocrectal cancer. Nat Rev Gastroenterol Hepatol. 2011;12:686–700.CrossRefGoogle Scholar
  40. 40.
    Anton R, Chatterjee SS, Simunda J, Cowin P, Dasgupta R. A systematic screen for micro-RNAs regulating the canonical Wnt pathway. PLoS One. 2011;10:e26257.CrossRefGoogle Scholar
  41. 41.
    Lujambio A, Esteller M. CpG island hypermethylation of tumor suppressor microRNAs in human cancer. Cell Cycle. 2007;6:1455–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Agirre X, Vilas-Zornoza A, Jimenez-Velasco A, Martin-Subero JI, Cordeu L, Garate L, 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;69:4443–53.PubMedCrossRefGoogle Scholar
  43. 43.
    Wong KY, So CC, Loong F, Chung LP, Lam WW, Liang R, et al. Epigenetic inactivation of the miR-124-1 in haematological malignancies. PLoS One. 2011;6:e19027.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Wilting SM, van Boerdonk RA, Henken FE, Meijer CJ, Diosdado B, Meijer GA, et al. Methylation-mediated silencing and tumour suppressive function of hsa-miR-124 in cervical cancer. Mol Cancer. 2010;9:1–14. doi: 10.1186/1476-4598-9-167.Google Scholar
  45. 45.
    Zheng F, Liao YJ, Cai MY, Liu YH, Liu TH, Chen SP, et al. The putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2. Gut. 2012;2:278–89.CrossRefGoogle Scholar
  46. 46.
    Lehmann U, Hasemeier B, Christgen M, Muller M, Romermann D, Langer F, et al. Epigenetic inactivation of microRNA gene hsa-mir-9-1 in human breast cancer. J Pathol. 2008;214:17–24.PubMedCrossRefGoogle Scholar
  47. 47.
    Omura N, Li CP, Li A, Hong SM, Walter K, Jimeno A, et al. Genome-wide profiling of methylated promoters in pancreatic adenocarcinoma. Cancer Biol Ther. 2008;7:1146–56.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Bandres E, Agirre X, Bitarte N, Ramirez N, Zarate R, Roman-Gomez J, et al. Epigenetic regulation of microRNA expression in colorectal cancer. Int J Cancer. 2009;125:2737–43.PubMedCrossRefGoogle Scholar
  49. 49.
    Hildebrandt MA, Gu J, Lin J, Ye Y, Tan W, Tamboli P, 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;29:5724–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Tsai KW, Liao YL, Wu CW, Hu LY, Li SC, Chan WC, et al. Aberrant hypermethylation of miR-9 genes in gastric cancer. Epigenetics. 2011;6:1189–97.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Rodriguez-Otero P, Roman-Gomez J, Vilas-Zornoza A, Jose Eneriz ES, Martin-Palanco V, Rifon J, et al. Deregulation of FGFR1 and CDK6 oncogenic pathways in acute lymphoblastic leukaemia harbouring epigenetic modifications of the MIR9 family. Br J Haematol. 2010;1:73–83.Google Scholar
  52. 52.
    Rotkrua P, Akiyama Y, Hashimoto Y, Otsubo T, Yuasa Y. Mir-9 downregulation CDX2 expression in gastric cancer cells. Int J Cancer. 2011;11:2611–20.CrossRefGoogle Scholar
  53. 53.
    Ma L, Young J, Prabhala MV, Pan E, Mestdagh P, Muth D, et al. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010;3:247–56.Google Scholar
  54. 54.
    Chen X, Hu H, Guan X, Xiong G, Wang Y, Wang K, Li J, et al. CpG island methylation status of miRNAs in esophageal squamous cell carcinoma. Int J Cancer. 2012;130:1607–13.PubMedCrossRefGoogle Scholar
  55. 55.
    Kozaki K, Imoto I, Mogi S, Omura K, Inazawa J. Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Res. 2008;68:2094–105.PubMedCrossRefGoogle Scholar
  56. 56.
    Lujambio A, Calin GA, Villanueva A, Ropero S, Sanchez-Cespedes M, Blanco D, Lujambio A, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci U S A. 2008;105:13556–61.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K, Shinomura 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;68:4123–32.PubMedCrossRefGoogle Scholar
  58. 58.
    Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22:894–907.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Davalos V, Moutinho C, Villanueva A, Boque R, Silva P, Carneiro F, et al. Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis. Oncogene. 2012;31:2062–74.PubMedCrossRefGoogle Scholar
  60. 60.
    Althoff K, Beckers A, Odersky A, Mestdagh P, Köster J, Bray IM, et al. MiR-137 functions as a tumor suppressor in neuroblastoma by downregulating KDM1A. Int J Cancer. 2013;5:1064–673.CrossRefGoogle Scholar
  61. 61.
    Denis H, Van Grenbergen O, Delatte B, Dedeurwaerder S, Putmans S, Calonne E, et al. MicroRNAs regulate KDM5 histone demethylases in breast cancer cells. Mol Biosyst. 2015;12:404–13.CrossRefGoogle Scholar
  62. 62.
    Ren X, Bai X, Zhang X, Li Z, Tang L, Zhao X, et al. Quantitative nuclear proteomics identifies that miR-137-mediated EZH2 reduction regulates resveratrol-induced apoptosis of neuroblastoma cells. Mol Cell Proteomics. 2015;2:316–28.CrossRefGoogle Scholar
  63. 63.
    Balaguer F, Link A, Lozano JJ, Cuatrecasas M, Nagasaka T, Boland RC, et al. Epigenetic silencing of miR-137 is an early event in colorectal carcinogenesis. Cancer Res. 2010;70:6609–18.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Datta J, Kutay H, Nasser MW, Nuovo GJ, Wang B, Majumder S, et al. Methylation mediated silencing of MicroRNA-1 gene and its role in hepatocellular carcinogenesis. Cancer Res. 2008;68:5049–58.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Rao PK, Missiaglia E, Shields L, Hyde G, Yuan B, Shepherd CJ, et al. Distinct roles for miR-1 and miR-133a in the proliferation and differentiation of rhabdomyosarcoma cells. FASEB J. 2010;24:3427–37.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Lanza G, Ferracin M, Gafa R, Veronese A, Spizzo R, Pichiorri F, et al. mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer. Mol Cancer. 2007;6:54.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Earle JS, Luthra R, Romans A, Abraham R, Ensor J, Yao H, et al. Association of microRNA expression with microsatellite instability status in colorectal adenocarcinoma. J Mol Diagn. 2010;12:433–40.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Kaur S, Lotsari JE, Al-Sohaily S, Warusavitarne J, Kohonen-Corish MR, Peltomaki P. Identification of subgroup-specific miRNA patterns by epigenetic profiling of sporadic and Lynch syndrome-associated colorectal and endometrial carcinoma. Clin Epigenetics. 2015;7:20. doi: 10.1186/s13148-015-0059-3.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS. Non-coding RNAs: regulators of disease. J Pathol. 2010;2:126–39.CrossRefGoogle Scholar
  70. 70.
    Di Ruscio A, Ebralidze AK, Benoukraf T, Amabile G, Goff LA, Terragni J, et al. DNMT1-interacting RNAs block gene-specific DNA methylation. Nature. 2013;503:371–6.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Merry CR, Forrest ME, Sabers JN, Beard L, Gao XH, Hatzoglou M, et al. DNMT1-associated long non-coding RNAs regulate global gene expression and DNA methylation in colon cancer. Hum Mol Genet. 2015;24:6240–53.PubMedCrossRefGoogle Scholar
  72. 72.
    Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, 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;106:11667–72.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA, 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;9:435–43.PubMedCrossRefGoogle Scholar
  74. 74.
    Tanaka T, Arai M, Wu S, Kanda T, Miyauchi H, Imazeki F, et al. Epigenetic silencing of microRNA-373 plays an important role in regulating cell proliferation in colon cancer. Oncol Rep. 2011;26:1329–35.PubMedGoogle Scholar
  75. 75.
    Tang JT, Wang JL, Du W, Hong J, Zhao SL, Wang YC, et al. MicroRNA 345, a methylation-sensitive microRNA is involved in cell proliferation and invasion in human colorectal cancer. Carcinogenesis. 2011;32:1207–15.PubMedCrossRefGoogle Scholar
  76. 76.
    Lv LV, Zhou J, Lin C, Hu G, Yi LU, DU J, et al. DNA methylation is involved in the aberrant expression of miR-133b in colorectal cancer cells. Oncol Lett. 2015;10:907–12.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Hashimoto Y, Akiyama Y, Otsubo T, Shimada S, Yuasa Y. Involvement of epigenetically silenced microRNA-181c in gastric carcinogenesis. Carcinogenesis. 2010;31:777–84.PubMedCrossRefGoogle Scholar
  78. 78.
    Saito Y, Suzuki H, Tsugawa H, Nakagawa I, Matsuzaki J, Kanai Y, et al. Chromatin remodeling at Alu repeats by epigenetic treatment activates silenced microRNA-512-5p with downregulation of Mcl-1 in human gastric cancer cells. Oncogene. 2009;28:2738–44.PubMedCrossRefGoogle Scholar
  79. 79.
    Yan H, Choi AJ, Lee BH, Ting AH. Identification and functional analysis of epigenetically silenced microRNAs in colorectal cancer cells. PLoS One. 2011;6:e20628.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Shen J, Wang S, Siegel AB, Remotti H, Wang Q, Sirosh I, et al. Genome-Wide Expression of MicroRNAs Is Regulated by DNA Methylation in Hepatocarcinogenesis. Gastroenterol Res Pract. 2015;2015:1–12.Google Scholar
  81. 81.
    Vrba L, Munoz-Rodriguez JL, Stampfer MR, Futscher BW, et al. miRNA gene promoters are frequent targets of aberrant DNA methylation in human breast cancer. PLoS One. 2013;8:e54398.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Nygren AO, Ameziane N, Duarte HMB, Vijzelaar RNCP, Waisfisz Q, Hess CJ, et al. Methylation-specific MLPA (MS-MLPA): simultaneous detection of CpG methylation and copy number changes of up to 40 sequences. Nucleic Acids Res. 2005;33:e128.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Nieminen TT, Gylling A, Abdel-Rahman WM, Nuorva K, Aarnio M, Renkonen-Sinisalo L, et al. Molecular analysis of endometrial tumorigenesis: importance of complex hyperplasia regardless of atypia. Clin Cancer Res. 2009;15:5772–83.PubMedCrossRefGoogle Scholar
  84. 84.
    Suijkerbuijk KP, Pan X, van der Wall E, van Diest PJ, Vooijs M. Comparison of different promoter methylation assays in breast cancer. Anal Cell Pathol. 2010;33:274–6.CrossRefGoogle Scholar
  85. 85.
    Homig-Holzel C, Savola S. Multiplex ligation-dependent amplification (MLPA) in tumor diagnostics and prognostics. Diagn Mol Pathol. 2012;4:189–206.CrossRefGoogle Scholar
  86. 86.
    Tournier B, Chapusot C, Courcet E, Martin L, Lepage C, Faivre J, et al. Why do results conflict regarding the prognostic value of the methylation status on colon cancer? The role of the preservation method. BMC Cancer. 2012;12:1–12.CrossRefGoogle Scholar
  87. 87.
    Xiong Z, Laird PW. COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Res. 1997;12:2532–4.CrossRefGoogle Scholar
  88. 88.
    Morita S, Takahashi RU, Yamashita R, Toyoda A, Horii T, Kimura M, et al. Genome-wide analysis of DNA methylation and expression of microRNAs in breast cancer cells. Int J Mol Sci. 2012;13:8259–72.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Zhao Y, Sun J, Zhang H, Guo S, Gu J, Wang W, et al. High-frequency aberrantly methylated targets in pancreatic adenocarcinoma identified via global DNA methylation analysis using methylCap-seq. Clin Epigenetics. 2014;6:18.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Tsuruta T, Kozaki K, Uesugi A, Furuta M, Hirasawa A, Imoto I, et al. miR-152 is a tumor suppressor microRNA that is silenced by DNA hypermethylation in endometrial cancer. Cancer Res. 2011;71:6450–62.PubMedCrossRefGoogle Scholar
  91. 91.
    Uesugi A, Kozaki K, Tsuruta T, Furuta M, Morita K, Imoto I, et al. The tumor suppressive microRNA miR-218 targets the mTOR component Rictor and inhibits AKT phosphorylation in oral cancer. Cancer Res. 2011;71:5765–78.PubMedCrossRefGoogle Scholar
  92. 92.
    Kong YW, Ferland-McCollough D, Jackson TJ, Bushell M. microRNAs in cancer management. Lancet Oncol. 2012;6:e249–58.CrossRefGoogle Scholar
  93. 93.
    Iorio MV, Croce CM. MicroRNA dysregulation in cancer, diagnostics, monitoring and therapeutics. A comprehensive review. Mol Med. 2012;3:143–59.Google Scholar
  94. 94.
    Wang Z, Chen Z, Gao Y, Li N, Li B, Tan F, et al. DNA hypermethylation of microRNA-34b/c has prognostic value for stage non-small cell lung cancer. Cancer Biol Ther. 2011;11:490–6.PubMedCrossRefGoogle Scholar
  95. 95.
    Roman-Gomez J, Agirre X, Jimenez-Velasco A, Arqueros V, Vilas-Zornoza A, Rodriguez-Otero P, et al. Epigenetic regulation of microRNAs in acute lymphoblastic leukemia. J Clin Oncol. 2009;27:1316–22.PubMedCrossRefGoogle Scholar
  96. 96.
    Kitano K, Watanabe K, Emoto N, Kage H, Hamano E, Nagase T, et al. CpG island methylation of microRNAs is associated with tumor size and recurrence of non-small-cell lung cancer. Cancer Sci. 2011;12:2126–31.CrossRefGoogle Scholar
  97. 97.
    Grady WM, Parkin RK, Mitchell PS, Lee JH, Kim YH, Tsuchiya KD, et al. Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer. Oncogene. 2008;27:3880–8.PubMedCrossRefGoogle Scholar
  98. 98.
    Deng G, Kakar S, Kim YS. MicroRNA-124a and microRNA-34b/c are frequently methylated in all histological types of colorectal cancer and polyps, and in the adjacent normal mucosa. Oncol Lett. 2011;2:175–80.PubMedGoogle Scholar
  99. 99.
    Kalimutho M, Di Cecilia S, Del Vecchio BG, Roviello F, Sileri P, Cretella M, et al. Epigenetically silenced miR-34b/c as a novel faecal-based screening marker for colorectal cancer. Br J Cancer. 2011;104:1770–8.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Yin Y, Zhang B, Wang W, Fei B, Quan C, Zhang J, et al. miR-204-5p inhibits proliferation and invasion and enhances chemotherapeutic sensitivity of colorectal cancer cells by downreagulating RAB22A. Clin Cancer Res. 2014;23:6187–99.CrossRefGoogle Scholar
  101. 101.
    Cheasley D, Jorissen RN, Liu S, et al. Genomic approach to translational studies in colorectal cancer. Transl Cancer Res. 2015;4:235–55.Google Scholar
  102. 102.
    Ji Q, Hao X, Zhang M, Tang W, Yang M, Li L, et al. MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS One. 2009;4:e6816.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Okugawa Y, Grady WM, Goel A. Epigenetic alterations in colorectal cancer: emerging biomarkers. Gastroenterology. 2015;5:1204–25.CrossRefGoogle Scholar
  104. 104.
    Duursma AM, Kedde M, Schrier M, le Sage C, Agami R. miR-148 targets human DNMT3b protein coding region. RNA. 2008;5:872–7. doi: 10.1261/rna.972008.CrossRefGoogle Scholar
  105. 105.
    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;3:881–90. doi: 10.1002/hep.23381.Google Scholar
  106. 106.
    Varambally S, Cao Q, Mani RS, Shankar S, Wang X, Ateeq B, et al. Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science. 2008;322:1695–9. doi: 10.1126/science.1165395.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, et al. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet. 2006;38:228–33.PubMedCrossRefGoogle Scholar
  108. 108.
    Noonan EJ, Place RF, Pookot D, Basak S, Whitson JM, Hirata H, et al. miR-449a targets HDAC-1 and induces growth arrest in prostate cancer. Oncogene. 2009;14:1714–24. doi: 10.1038/onc.2009.19.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Sippy Kaur
    • 1
    Email author
  • Johanna E. Lotsari-Salomaa
    • 2
  • Riitta Seppänen-Kaijansinkko
    • 1
  • Päivi Peltomäki
    • 2
  1. 1.Department of Oral and Maxillofacial DiseasesUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
  2. 2.Department of Medical and Clinical GeneticsUniversity of HelsinkiHelsinkiFinland

Personalised recommendations