人类肝癌细胞中ECM1,ATF5,和EOMES的DNA甲基化和羟甲基化揭示肿瘤抑制作用的综合分析 Integrated analyses of DNA methylation and hydroxym

研究对象：人
发表期刊：Genome Biology
发表时间：2014年12月

摘要
Differences in 5-hydroxymethylcytosine, 5hmC, distributions may complicate previous observations of abnormal cytosine methylation statuses that are used for the identification of new tumor suppressor gene candidates that are relevant to human hepatocarcinogenesis. The simultaneous detection of 5-methylcytosine and 5-hydroxymethylcytosine is likely to stimulate the discovery of aberrantly methylated genes with increased accuracy in human hepatocellular carcinoma. Here, we performed ultra-performance liquid chromatography/tandem mass spectrometry and single-base high-throughput sequencing, Hydroxymethylation and Methylation Sensitive Tag sequencing, HMST-seq, to synchronously measure these two modifications in human hepatocellular carcinoma samples. After identification of differentially methylated and hydroxymethylated genes in human hepatocellular carcinoma, we integrate DNA copy-number alterations, as determined using array-based comparative genomic hybridization data, with gene expression to identify genes that are potentially silenced by promoter hypermethylation. : We report a high enrichment of genes with epigenetic aberrations in cancer signaling pathways. Six genes were selected as tumor suppressor gene candidates, among which, ECM1, ATF5 and EOMES are confirmed via siRNA experiments to have potential anti-cancer functions
关键词
人 ；抑癌候选基因 ；超高效液相色谱/串联；DNA拷贝数变化；

人

背景

肝炎病毒B和C，酒精滥用是引起肝细胞癌变的重要原因。肝癌是世界范围内最常见的原发性肝癌和全球第三大癌症死亡的原因。越来越多的遗传改变如：染色体异常，基因扩增，基因突变与肝癌的发生相关已被广泛接受。此外，表观遗传学的改变，特别是DNA的5‘端胞嘧啶的异常甲基化，已被广泛研究。在肿瘤细胞中的DNA甲基化被认为可以导致染色体不稳定和癌基因的激活，已普遍被认为是癌症的一个非常稳定的临床标志物。更重要的是，许多研究报道，抑癌基因的甲基化（抑癌基因）有助于肝癌发病。因此，DNA甲基化的检测可以提供强大的机械洞察肝癌发生可能对肝癌的临床诊断的一个潜在的应用。
## 研究结果： ##

1. 肝癌细胞中的基因组CCGG位点中，5mc水平总体增加但是5hmc水平总体降低。