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Androgen receptor drives hepatocellular carcinogenesis by activating enhancer of zeste homolog 2-mediated Wnt/beta-catenin signaling 期刊论文

编号：

a6291da2-dde6-4773-8600-33644d2b0743
作者：

Song, Haibin#^[1]Yu, Zhuo(余卓)#^[2]Sun, Xuehua(孙学华)^[2]Feng, Jun^[3];Yu, Qi^[3];Khan, Hanif^[3];Zhu, Xiaojun^[2];Huang, Lingying^[2];Li, Man(李曼)^[2]Mok, Myth T. S.^[4];Cheng, Alfred S. L.*^[4]Gao, Yueqiu(高月求)*^[2]Feng, Hai*^[3]
语种：

英文
期刊：

EBIOMEDICINE ISSN：2352-3964 2018 年 35 卷 (155 - 166) ; SEP
收录：
关键词：

Androgen receptor EZH2 Wnt/beta-catenin signaling Hepatocarcinogenesis Epigenetics
摘要：

Background: Androgen receptor (AR) plays a crucial role as a transcription factor in promoting the development of hepatocellular carcinoma (HCC) which is prone to aberrant chromatin modifications. However, the regulatory effects of AR on epigenetic mediators in HCC remain ill-defined. Enhancer of zeste homolog 2 (EZH2), an oncogene responsible for the tri-methylation of histone H3 at lysine 27 (H3K27me3), was identified to be overexpressed in approximate 70-90% of HCC cases, which prompted us to investigate whether or how AR regulates EZH2 expression.
Methods: Colony formation, soft agar assay, xenograft and orthotopic mouse models were used to determine cell proliferation and tumorigenicity of gene-manipulated HCC cells. Gene regulation was assessed by chromatin immunoprecipitation, luciferase reporter assay, quantitative RT-PCR and immunoblotting. Clinical relevance of candidate proteins in patient specimens was examined in terms of pathological parameters and postsurgical survival rates.
Findings: In this study, we found that AR upregulated EZH2 expression by binding to EZH2 promoter and stimulating its transcriptional activity. EZH2 overexpression increased H3K27me3 levels and thereby silenced the expression of Wnt signal inhibitors, resulting in activation of Wnt/beta-catenin signaling and subsequently induction of cell proliferation and tumorigenesis. In a cohort of human HCC patients, concordant overexpression of AR, EZH2. H3K27me3 and active beta-catenin was observed in tumor tissues compared with paired non-tumor tissues, which correlated with tumor progression and poor prognosis. These findings demonstrate a novel working model in which EZH2 mediates AR-induced Wnt/beta-catenin signaling activation through epigenetic modification, and support the application of EZH2-targeted reagents for treating HCC patients. (C) 2018 The Authors. Published by Elsevier B.V.
推荐引用方式
GB/T 7714：

Song Haibin,Yu Zhuo,Sun Xuehua, et al. Androgen receptor drives hepatocellular carcinogenesis by activating enhancer of zeste homolog 2-mediated Wnt/beta-catenin signaling [J].EBIOMEDICINE,2018,35:155-166.
APA：

Song Haibin,Yu Zhuo,Sun Xuehua,Feng Jun,&Feng Hai.(2018).Androgen receptor drives hepatocellular carcinogenesis by activating enhancer of zeste homolog 2-mediated Wnt/beta-catenin signaling .EBIOMEDICINE,35:155-166.
MLA：

Song Haibin, et al. "Androgen receptor drives hepatocellular carcinogenesis by activating enhancer of zeste homolog 2-mediated Wnt/beta-catenin signaling" .EBIOMEDICINE 35(2018):155-166.
入库时间：

1/6/2020 6:08:40 PM
更新时间：

1/6/2020 6:08:40 PM
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