title: The role of EZH2 and DNA methylation in hMLH1 silencing in epithelial ovarian cancer.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Wang
authors.forename: Lili
authors.initials: L
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.forename: Jinghui
authors.initials: J
authors.lastname: Jia
authors.forename: Yanping
authors.initials: Y
authors.lastname: Gao
authors.forename: Minglin
authors.initials: M
authors.lastname: Liang
authors.forename: Zehua
authors.initials: Z
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D015153:Blotting, Western; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D000070957:MutL Protein Homolog 1