DNA甲基化在胃癌中的研究进展
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摘要
胃癌发生和进展是多因素、多基因、多步骤参与的复杂分子机制调控过程,其中DNA甲基化研究为深入了解胃癌的发病机制提供了新的思路和方向。肿瘤相关基因甲基化失衡导致的基因激活或失活与胃癌的发生、进展密切相关。抑癌基因启动子区高甲基化是胃癌发生的重要机制,可与之发生在同一肿瘤中的变化还包括局部CpG岛高甲基化和整个基因组广泛低甲基化。胃癌相关基因启动子区CpG岛甲基化异常改变对其表达造成的影响可稳定遗传给子代细胞。目前DNA甲基化作为潜在可行的肿瘤生物标志物为胃癌的发生和进展提供了一个合理的分子机制解释而引起了广泛的关注。笔者就目前胃癌研究领域常见DNA甲基化研究报道作一综述,以期阐明DNA甲基化在胃癌发生及进展中的意义和价值。
引文
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[2]Ferlay J,Steliarova-Foucher E,Lortet-Tieulent J,et al.Cancer incidence and mortality patterns in Europe:estimates for 40countries in 2012[J].Eur J Cancer,2013,49(6):1374
[3]Stutes M,Tran S,Demorrow S.Genetic and epigenetic changes associated with cholangiocarcinoma:from DNA methylation to microRNAs[J].World J Gastroenterol,2007,13(48):6465
[4]Tischoff I,Wittekind C,Tannapfel A.Role of epigenetic alterations in cholangiocarcinoma[J].J Hepatobiliary Pancreat Surg,2006,13(4):274
[5]Isomoto H.Epigenetic alterations associated with cholangiocarcinoma(review)[J].Oncol Rep,2009,22(2):227
[6]Waddington C H.Preliminary Notes on the Development of the Wings in Normal and Mutant Strains of Drosophila[J].Proc Natl A-cad Sci U S A,1939,25(7):299
[7]Cervoni N,Bhattacharya S,Szyf M.DNA demethylase is a processive enzyme[J].J Biol Chem,1999,274(13):8363
[8]Gaudet F,Hodgson J G,Eden A,et al.Induction of tumors in mice by genomic hypomethylation[J].Science,2003,300(5618):489
[9]Dodge J E,Okano M,Dick F,et al.Inactivation of Dnmt3b in mouse embry onic fibroblasts results in DNA hypomethylation,chromosomal instability,and spontaneous immortalization[J].J Biol Chem,2005,280(18):17986
[10]Goto T,Mizukami H,Shirahata A,et al.Methylation of the p16 gene is frequently detected in lymphatic-invasive gastric cancer[J].Anticancer Res,2010,30(7):2701
[11]Ding Y,Le XP,Zhang Q X,et al.Methylation and mutation analysis of p16 gene in gastric cancer[J].World J Gastroenterol,2003,9(3):423
[12]Barberis A,Superti-Furga G,Vitelli L,et al.Developmental and tissue-specific regulation of a novel transcription factor of the sea urchin[J].Genes Dev,1989,3(5):663
[13]Li X,Cheung K F,Ma X,et al.Epigenetic inactivation of paired box gene 5,a novel tumor suppressor gene,through direct upregulation of p53 is associated with prognosis in gastric cancer patients[J].Oncogene,2012,31(29):3419
[14]Sugita H,Iida S,Inokuchi M,et al.Methylation of BNIP3 and DAPKindicates lower response to chemotherapy and poor prognosis in gastric cancer[J].Oncol Rep,2011,25(2):513
[15]Jia W,Yu T,Cao X,et al.Clinical effect of DAPK promoter methylation in gastric cancer[J].Medicine,2016,95(43):e5040
[16]Cheung K F,Lam C N,Wu K,et al.Characterization of the gene structure,functional significance,and clinical application of RNF180,a novel gene in gastric cancer[J].Cancer,2012,118(4):947
[17]Xie X M,Deng J Y,Hou Y C,et al.Evaluating the clinical feasibility:The direct bisulfite genomic sequencing for examination of methylated status of E3 ubiquitin ligase RNF180 DNA promoter to predict the survival of gastric cancer[J].Cancer Biomark,2015,15(3):259
[18]Wang N,Sui F,Ma J,et al.Site-specific Hypermethylation of RUNX3Predicts Poor Prognosis in Gastric Cancer[J].Arch Med Res,2016,47(4):285
[19]Chen W,Gao N,Shen Y,et al.Hypermethylation downregulates Runx3 gene expression and its restoration suppresses gastric epithelial cell growth by inducing p27 and caspase3 in human gastric cancer[J].J Gastroenterol Hepatol,2010,25(4):823
[20]Wang S,Kang W,Go M Y,et al.Dapper homolog 1 is a novel tumor suppressor in gastric cancer through inhibiting the nuclear factorkappaB signaling pathway[J].Mol Med,2012,18:1402
[21]Hou J,Wen Y H,Feng K N,et al.DACT1 is involved in human placenta development by promoting Wnt signaling[J].Arch Gynecol Obstet,2015,291(6):1289
[22]Yin X,Xiang T,Li L,et al.DACT1,an antagonist to Wnt/betacatenin signaling,suppresses tumor cell growth and is frequently silenced in breast cancer[J].Breast Cancer Res,2013,15(2):R23
[23]Schubert F R,Sobreira D R,Janousek R G,et al.Dact genes are chordate specific regulators at the intersection of Wnt and Tgf-beta signaling pathways[J].BMC Evol Biol,2014,14:157
[24]Cheng H,Deng Z,Wang Z,et al.The role of aberrant promoter hypermethylation of DACT1 in bladder urothelial carcinoma[J].JBiomed Res,2012,26(5):319
[25]Yau T O,Chan C Y,Chan K L,et al.HDPR1,a novel inhibitor of the WNT/beta-catenin signaling,is frequently downregulated in hepatocellular carcinoma:involvement of methylation-mediated gene silencing[J].Oncogene,2005,24(9):1607
[26]Yang Z Q,Zhao Y,Liu Y,et al.Downregulation of HDPR1 is associated with poor prognosis and affects expression levels of p120-catenin and beta-catenin in nonsmall cell lung cancer[J].Mol Carcinog,2010,49(5):508
[27]Deng J,Liang H,Zhang R,et al.Methylated Cp G site count of dapper homolog 1(DACT1)promoter prediction the poor survival of gastric cancer[J].Am J Cancer Res,2014,4(5):518
[28]Katoh M,Katoh M.Identification and characterization of human DAPPER1 and DAPPER2 genes in silico[J].Int J Oncol,2003,22(4):907
[29]Luo J,Li Y N,Wang F,et al.S-adenosylmethionine inhibits the growth of cancer cells by reversing the hypomethylation status of cmyc and H-ras in human gastric cancer and colon cancer[J].Int JBiol Sci,2010,6(7):784
[30]Zhao Y,Li J S,Guo M Z,et al.Inhibitory effect of S-adenosylmethionine on the growth of human gastric cancer cells in vivo and in vitro[J].Chin J Cancer,2010,29(8):752