Aberrant DNA methylation in human cancers

Abstract

DNA methylation, one of the best-characterized epigenetic modifications, plays essential roles in diseases, including human cancers. In recent years, our understanding on DNA methylation with human cancers has made significant progress, which was facilitated by stunning development in the analysis of the human methylome of multiple cancer types. In this review, recent developments in the characterization of aberrant DNA methylation involved in human cancers development were discussed with special emphasis on the mechanisms of aberrant DNA methylation in human cancers. We also summarize the recent treatment strategy for human cancers with de-methylation drugs.

Keywords

epigenetics / aberrant DNA methylation / human cancers / treatment

References

[1] EstellerM. Cancer epigenetics for the 21st century: What’s next?. Genes Cancer, 2011, 2(6): 604-606

[2] SharmaS, KellyTK, JonesPA. Epigenetics in cancer. Carcinogenesis, 2010, 31(1): 27-36

[3] EstellerM. Aberrant DNA methylation as a cancer-inducing mechanism. Annu Rev Pharmacol Toxicol, 2005, 45: 629-656

[4] DeatonAM, BirdA. CpG islands and the regulation of transcription. Genes Dev, 2011, 25(10): 1010-1022

[5] MedvedevaYA, FridmanMV, OparinaNJ, et al.. Intergenic, gene terminal, and intragenic CpG islands in the human genome. BMC Genomics, 2010, 11: 48

[6] LanJ, HuaS, HeX, et al.. DNA methyltransferases and methyl-binding proteins of mammals. Acta Biochim Biophys Sin (Shanghai), 2010, 42(4): 243-252

[7] Dhe-PaganonS, SyedaF, ParkL. DNA methyltransferase 1: regulatory mechanisms and implications in health and disease. Int J Biochem Mol Biol, 2011, 2(1): 58-66

[8] OkanoM, BellDW, HaberDA, et al.. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell, 1999, 99(3): 247-257

[9] ThiagarajanD, DevRR, KhoslaS. The DNA methyltranferase Dnmt2 participates in RNA processing during cellular stress. Epigenetics, 2011, 6(1): 103-113

[10] SuetakeI, ShinozakiF, MiyagawaJ, et al.. DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction. J Biol Chem, 2004, 279(26): 27 816-27 823

[11] EstellerM. CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future. Oncogene, 2002, 21(35): 5427-5440

[12] FournierA, SasaiN, NakaoM, et al.. The role of methyl-binding proteins in chromatin organization and epigenome maintenance. Brief Funct Genomics, 2012, 11(3): 251-264

[13] DefossezPA, StanchevaI. Biological functions of methyl-CpG-binding proteins. Prog Mol Biol Transl Sci, 2011, 101: 377-398

[14] AiT, CuiH, ChenL. Multi-targeted histone deacetylase inhibitors in cancer therapy. Curr Med Chem, 2012, 19(4): 475-487

[15] DasPM, SingalR. DNA methylation and cancer. J Clin Oncol, 2004, 22(22): 4632-4642

[16] KulisM, EstellerM. DNA methylation and cancer. Adv Genet, 2010, 70: 27-56

[17] ToranoEG, PetrusS, FernandezAF, et al.. Global DNA hypomethylation in cancer: review of validated methods and clinical significance. Clin Chem Lab Med, 2012, 50(10): 1733-1742

[18] Daura-OllerE, CabreM, MonteroMA, et al.. Specific gene hypomethylation and cancer: new insights into coding region feature trends. Bioinformation, 2009, 3(8): 340-343

[19] EhrlichM. DNA hypomethylation in cancer cells. Epigenomics, 2009, 1(2): 239-259

[20] HercegZ, UshijimaT. Introduction: epigenetics and cancer. Adv Genet, 2010, 70: 1-23

[21] DenisH, NdlovuMN, FuksF. Regulation of mammalian DNA methyltransferases: a route to new mechanisms. EMBO Rep, 2011, 12(7): 647-656

[22] FilipowiczW, BhattacharyyaSN, SonenbergN. Mechanisms of post-transcriptional regulation by micro- RNAs: are the answers in sight?. Nat Rev Genet, 2008, 9(2): 102-114

[23] FabbriM, GarzonR, CimminoA, et al.. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci USA, 2007, 104(40): 15 805-15 810

[24] GarzonR, LiuS, FabbriM, 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): 6411-6418

[25] DuursmaAM, KeddeM, SchrierM, et al.. miR-148 targets human DNMT3b protein coding region. RNA, 2008, 14(5): 872-877

[26] BraconiC, HuangNY, PatelT. MicroRNA-dependent regulation of DNA methyltransferase-1 and tumor suppressor gene expression by interleukin-6 in human malignant cholangiocytes. Hepatology, 2010, 51(3): 881-890

[27] HuangJ, WangY, GuoY, et al.. Down-regulated microRNA-152 induces aberrant DNA methylation in hepatitis B virus-related hepatocellular carcinoma by targeting DNA methyltransferase 1. Hepatology, 2010, 52(1): 60-70

[28] PanW, ZhuS, YuanM, et al.. MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J Immunol, 2010, 184(12): 6773-6781

[29] ZhaoS, WangY, LiangY, et al.. MicroRNA-126 regulates DNA methylation in CD4+ T cells and contributes to systemic lupus erythematosus by targeting DNA methyltransferase 1. Arthritis Rheum, 2011, 63(5): 1376-1386

[30] ChenBF, GuS, SuenYK, et al.. microRNA-199a-3p, DNMT3A, and aberrant DNA methylation in testicular cancer. Epigenetics, 2013, 9(1): 1-8

[31] KruegerKE, SrivastavaS. Posttranslational protein modifications: current implications for cancer detection, prevention, and therapeutics. Mol Cell Proteomics, 2006, 5(10): 1799-1810

[32] HannSR. Role of post-translational modifications in regulating c-Myc proteolysis, transcriptional activity and biological function. Semin Cancer Biol, 2006, 16(4): 288-302

[33] LiH, RauchT, ChenZX, et al.. The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells. J Biol Chem, 2006, 281(28): 19 489-19 500

[34] EstevePO, ChinHG, BennerJ, et al.. Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells. Proc Natl Acad Sci USA, 2009, 106(13): 5076-5081

[35] LavoieG, EstevePO, LaulanNB, et al.. PKC isoforms interact with and phosphorylate DNMT1. Bmc Biology, 2011, 9: 31

[36] LingY, SankpalUT, RobertsonAK, et al.. Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription. Nucleic Acids Res, 2004, 32(2): 598-610

[37] KangES, ParkCW, ChungJH. Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1. Biochem Biophys Res Commun, 2001, 289(4): 862-868

[38] LeeB, MullerMT. SUMOylation enhances DNA methyltransferase 1 activity. Biochem J, 2009, 421(3): 449-461

[39] WangJ, HeviS, KurashJK, et al.. The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nat Genet, 2009, 41(1): 125-129

[40] GlickmanJF, PavlovichJG, ReichNO. Peptide mapping of the murine DNA methyltransferase reveals a major phosphorylation site and the start of translation. J Biol Chem, 1997, 272(28): 17 851-17 857

[41] GoyalR, RathertP, LaserH, et al.. Phosphorylation of serine-515 activates the mammalian maintenance methyltransferase Dnmt1. Epigenetics, 2007, 2(3): 155-160

[42] KameshitaI, SekiguchiM, HamasakiD, et al.. Cyclin-dependent kinase-like 5 binds and phosphorylates DNA methyltransferase 1. Biochem Biophys Res Commun, 2008, 377(4): 1162-1167

[43] SugiyamaY, HatanoN, SueyoshiN, et al.. The DNA-binding activity of mouse DNA methyltransferase 1 is regulated by phosphorylation with casein kinase 1delta/epsilon. Biochem J, 2010, 427(3): 489-497

[44] HervouetE, LalierL, DebienE, et al.. Disruption of Dnmt1/PCNA/UHRF1 interactions promotes tumorigenesis from human and mice glial cells. PLoS One, 2010, 5(6): e11333

[45] NiessenHE, DemmersJA, VonckenJW. Talking to chromatin: post-translational modulation of polycomb group function. Epigenetics Chromatin, 2009, 2(1): 10

[46] RountreeMR, BachmanKE, HermanJG, et al.. DNA methylation, chromatin inheritance, and cancer. Oncogene, 2001, 20(24): 3156-3165

[47] GraffJR, HermanJG, LapidusRG, et al.. E-Cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res, 1995, 55(22): 5195-5199

[48] DuW, SearleJS. The rb pathway and cancer therapeutics. Curr Drug Targets, 2009, 10(7): 581-589

[49] ChengNC, BeitsmaM, ChanA, et al.. Lack of class I HLA expression in neuroblastoma is associated with high N-myc expression and hypomethylation due to loss of the MEMO-1 locus. Oncogene, 1996, 13(8): 1737-1744

[50] ChengNC, ChanAJK, BeitsmaMM, et al.. A human modifier of methylation for class I HLA genes (MEMO-1) maps to chromosomal bands 1p35–36.1. Hum Mol Genet, 1996, 5(3): 309-317

[51] WuJJ, IssaJP, HermanJ, et al.. Expression of an exogenous eukaryotic DNA methyltransferase gene induces transformation of Nih-3t3 cells. Proc Natl Acad Sci USA, 1993, 90(19): 8891-8895

[52] VertinoPM, YenRWC, GaoJ, et al.. De novo methylation of CpG island sequences in human fibroblasts overexpressing DNA (cytosine-5)-methyltransferase. Mol Cell Biol, 1996, 16(8): 4555-4565

[53] RountreeMR, BachmanKE, BaylinSB. DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nat Genet, 2000, 25(3): 269-277

[54] KennedyBK, BarbieDA, ClassonM, et al.. Nuclear organization of DNA replication in primary mammalian cells. Genes Dev, 2000, 14(22): 2855-2868

[55] HarbourJW, DeanDC. The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev, 2000, 14(19): 2393-2409

[56] HarbourJW, DeanDC. Chromatin remodeling and Rb activity. Curr Opin Cell Biol, 2000, 12(6): 685-689

[57] SahinM, SahinE, GumusluS, et al.. DNA methylation or histone modification status in metastasis and angiogenesis-related genes: a new hypothesis on usage of DNMT inhibitors and S-adenosylmethionine for genome stability. Cancer Metastasis Rev, 2010, 29(4): 655-676

[58] JonesPA, TaylorSM. Cellular differentiation, cytidine analogs and DNA methylation. Cell, 1980, 20(1): 85-93

[59] GoffinJ, EisenhauerE. DNA methyltransferase inhibitors-state of the art. Ann Oncol, 2002, 13(11): 1699-1716

[60] El-OstaA. Review on epigenetics in cancer gene therapy: series I. Cancer Gene Therapy, 2005, 12(8): 663-664

[61] ChengJC, YooCB, WeisenbergerDJ, et al.. Preferential response of cancer cells to zebularine. Cancer Cell, 2004, 6(2): 151-158

[62] Segura-PachecoB, Trejo-BecerrilC, Perez-CardenasE, et al.. Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy. Clin Cancer Res, 2003, 9(5): 1596-1603

[63] YanL, NassSJ, SmithD, et al.. Specific inhibition of DNMT1 by antisense oligonucleotides induces re-expression of estrogen receptor alpha (ER) in ER-negative human breast cancer cell lines. Cancer Biol Therapy, 2003, 2(5): 552-556

[64] TanJ, YangXJ, ZhuangL, et al.. Pharmacologic disruption of polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev, 2007, 21(9): 1050-1063

[65] Gal-YamEN, SaitoY, EggerG, et al.. Cancer epigenetics: Modifications, screening, and therapy. Ann Rev Med, 2008, 59: 267-280

[66] HuangY, GreeneE, StewartTM, et al.. Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes. Proc Natl Acad Sci USA, 2007, 104(19): 8023-8028

[67] LohYH, ZhangW, ChenX, et al.. Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells. Genes Dev, 2007, 21(20): 2545-2557

[68] DecarloD, HaddenMK. Oncoepigenomics: Making histone lysine methylation count. Eur J Med Chem, 2012, 56: 179-194

[69] Akhavan-NiakiH, SamadaniAA. DNA methylation and cancer development: Molecular mechanism. Cell Biochem Biophys, 2013, 67(2): 501-513