基于hMeDIP-seq分析肝癌小鼠癌组织中肝癌相关信号分子基因的羟甲基化  

Analysis of Hydroxylmethylation of Genes Involved in the Pathways in Hepatocellular Carcinoma of Mice Based on hMeDIP-seq

作　　者：李根亮[1] 许苡侥 卢舒雨 黄晓敏[1] 农嵩[1] 蒋利和[2] 

机构地区：[1]右江民族医学院,百色533000 [2]广西大学动物科学与技术学院,南宁530004

出　　处：《基因组学与应用生物学》2016年第11期2872-2880,共9页Genomics and Applied Biology

基　　金：国家自然科学基金(No.3120365);广西自然科学基金(No.2015GXNSFAA139219);2013年度广西高校科学技术研究项目(桂教科研[2013]7号;No.2013YB185);右江民族医学院博士科研启动基金项目;广西大学博士后启动项目(No.XBZ130082);广西自治区级大学生创新创业训练计划项目(桂教高教[2016]41号;No.201610599039和No.201610599051;右医院字[2012]23号;No.QJCX201321和No.QJCX201334);右江民族医学院校级大学生创新创业训练计划项目(右医教字[2014]5号;No.XJCXB201412;No.XJCXB201420和No.XJCXB201423)共同资助

摘　　要：本研究通过hMeDIP-Seq技术和生物信息学分析,从肝细胞癌模型小鼠肝癌组织和肝组织基因组羟甲基化的角度研究肝癌相关信号通路,以期探讨肝癌相关信号分子基因的羟甲基化分布及其与基因表达的关系。研究结果表明,肝癌组织中共有52个具有显著统计学意义的肝癌相关信号分子基因发生了羟(FDR<0.05),而肝组织的则没有出现有统计学意义的相关羟甲基化信号分子基因。而且,这些信号分子基因的羟甲基化位点全部分布在基因表达的调控区域(外显子外),包括启动子-转录启始位点区、内含子区和基因间区。由于DNA羟甲基化是激活基因表达的重要手段,因此,这些区域的羟甲基化表明这些基因在肝癌组织中处于激活状态,并得到了RT-q PCR实验的抽样证明。由此可见,肝癌组织基因组上发生的羟甲基化与肝癌相关;它们通过激活大量的信号分子基因引起肝癌相关信号通路的异常活化,从而引起肝癌的发生或迁移。The purpose of the study is to explore the distribution of the hydroxylmethylated signaling molecule genes in hepatocellular carcinoma （HCC） and their relationship with the gene expression. We used both the cancer tissues and the liver tissues in the HCC model mice as the materials to study the signaling pathways of HCC with the hMeDIP-Seq technology and biological information analysis. The results showed that 52 signaling molecule genes that had notly statistical significances were hydroxylated （FDR〈0.05）, while none in the liver tissues. Moreover, all the hydroxylmethylated signaling molecular genes （except exon） were located in the regulatory regions of gene expression, including the promoter region, intron region and intergenic region. The hydroxylmethylation in the cancer tissues indicated that those genes were activated in those tissues since the hydroxylmethylation of DNA was an important way for the activation of gene expression, and it was proved by RT-qPCR experiment with sampling. Therefore, the hydroxylmethylation of the genome in the HCC tissues was related to the HCC and abnormally activated the signaling molecule genes, which may lead to the hepatocellular carcinogenesis or the metastasis of cancer cells.

关 键 词：hMeDIP—seq 肝癌 信号分子基因 DNA羟甲基化 

分 类 号：R735.7[医药卫生—肿瘤]