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

被引:12
作者
Wang, Junjie [1 ]
Yu, Lili [1 ]
Cai, Jing [1 ]
Jia, Jinghui [1 ]
Gao, Yanping [2 ]
Liang, Minglin [1 ]
Wang, Zehua [1 ]
机构
[1] Huazhong Univ Sci & Technol, Dept Obstet & Gynecol, Union Hosp, Tongji Med Coll, Wuhan 430074, Peoples R China
[2] First Hosp Datong, Dept Obstet & Gynecol, Datong, Peoples R China
基金
中国国家自然科学基金;
关键词
EZH2; hMLH1; Methylation; Epigenetics; Ovarian cancer; TUMOR-SUPPRESSOR GENES; MICROSATELLITE INSTABILITY; MISMATCH REPAIR; FRAMESHIFT MUTATIONS; DRUG-RESISTANCE; ZESTE HOMOLOG-2; BREAST-CANCER; COLON-CANCER; EXPRESSION; PROMOTER;
D O I
10.1016/j.bbrc.2013.03.037
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:470 / 476
页数:7
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