The role of EZH2 and DNA methylation in hMLH1 silencing in epithelial ovarian cancer

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• 作者：Junjie Wang^a ; ¹ ; Lili Yu^a ; ¹ ; Jing Cai^a ; Jinghui Jia^a ; Yanping Gao^b ; Minglin Liang^a ; Zehua Wang^a ; ^{zehuawang@163.net}
• 关键词：EZH2 ; hMLH1 ; Methylation ; Epigenetics ; Ovarian cancer
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2013
• 出版时间：19 April, 2013
• 年：2013
• 卷：433
• 期：4
• 页码：470-476
• 全文大小：2778 K

文摘

Enhancer of zeste homolog 2 (EZH2) is overexpressed in various malignancies and associated with poor prognosis and drug-resistance. A recent study suggested that there is a link between EZH2 expression and the mediation of gene silencing in association with aberrant DNA methylation. In the present study, we showed an inverse correlation between EZH2 and human mutL homolog 1 gene (hMLH1) expression in 30 epithelial ovarian cancer (EOC) tissues. Moreover, we found that EZH2 downregulation could induce the re-expression of the unmethylated, basally expressed hMLH1 gene without affecting DNA methylation in the hMLH1 promoter. These results suggest that EZH2 can modulate the transcription of basally expressed hMLH1 via a non-DNA-methylation-dependent pathway, but it has no effect on hMLH1 silencing that is mediated by DNA hypermethylation.