Integrated analysis of gene expression and DNA methylation changes induced by hepatocyte growth factor in human hepatocytes.
Integrated analysis of gene expression and DNA methylation changes induced by hepatocyte growth factor in human hepatocytes.
复制标题
肝细胞生长因子诱导人肝细胞基因表达及DNA甲基化变化的综合分析
DOI：
10.3892/mmr.2015.3974
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发表时间：
2015-09
影响因子：
3.4
通讯作者：
Yin ZY
中科院分区：
文献类型：
--
作者：
Xie CR;Sun H;Wang FQ;Li Z;Yin YR;Fang QL;Sun Y;Zhao WX;Zhang S;Zhao WX;Wang XM;Yin ZY
肝细胞癌是最常见的恶性肿瘤之一。肿瘤微环境不仅对肿瘤细胞的生长和存活具有支持作用，而且还可能引发肿瘤的复发和转移。肝细胞生长因子(HGF)是肿瘤微环境中重要的生长因子之一，在血管生成、肿瘤发生和再生中起重要作用。然而，HGF通过表观遗传重编程调控肝细胞癌的启动和发展的确切机制仍然不清楚。本研究主要针对肝细胞癌中肝细胞生长因子的表观遗传修饰和靶向抑癌基因进行了研究。表达谱分析和DNA甲基化阵列分别用于研究HGF的功能和检测整体基因组DNA甲基化的变化。基因表达和DNA甲基化的综合分析揭示了肝癌中潜在的肿瘤抑制基因(TSG)。目前的研究表明，HGF在肿瘤和非肿瘤途径以及整体基因组DNA甲基化变化中具有多种功能。HGF可上调DNA甲基转移酶1(DNMT1)的表达。DNMT1在肝细胞癌中的过度表达与其恶性潜能和预后不良有关。此外，基因表达和DNA甲基化变化的整合分析发现了新的潜在肿瘤抑制基因TSGs，包括MYOCD、PANX2和LHX9。本研究为HGF诱导的DNA高甲基化抑制TSGs的表观遗传提供了机制洞察。
Hepatocellular carcinoma (HCC) is the one of most common malignant tumors. The tumor microenvironment has a role in not only supporting growth and survival of tumor cells, but also triggering tumor recurrence and metastasis. Hepatocyte growth factor (HGF), one of the important growth factors in the tumor microenvironment, has an important role in angiogenesis, tumorigenesis and regeneration. However, the exact mechanism by which HGF regulates HCC initiation and development via epigenetic reprogramming has remained elusive. The present study focused on the epigenetic modification and target tumor-suppressive genes of HGF treatment in HCC. Expression profiling and DNA methylation array were performed to investigate the function of HGF and examine global genomic DNA methylation changes, respectively. Integrated analysis of gene expression and DNA methylation revealed potential tumor suppressor genes (TSGs) in HCC. The present study showed the multiple functions of HGF in tumorous and nontumorous pathways and global genomic DNA methylation changes. HGF treatment upregulated the expression of DNA methyltransferase 1 (DNMT1). Overexpression of DNMT1 in HCC patients correlated with the malignant potential and poor prognosis of HCC. Furthermore, integration analysis of gene expression and DNA methylation changes revealed novel potential tumor suppressor genes TSGs including MYOCD, PANX2 and LHX9. The present study has provided mechanistic insight into epigenetic repression of TSGs through HGF-induced DNA hypermethylation.