Androgen receptor drives hepatocellular carcinogenesis by activating enhancer of zeste homolog 2-mediated Wnt/β-catenin signaling

EBioMedicine
Haibin SongHai Feng

Abstract

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. 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. 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 activat...Continue Reading

Citations

May 10, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Na ShangWei Qiu
Jul 13, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Wei Qiu

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Methods Mentioned

BETA
immunoprecipitation
Transfection
PCR
Assay
xenograft
xenografts
ChIP
ChIP-PCR
ChIP-chip

Software Mentioned

GraphPad Prism
BandScan
GraphPad

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