Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma

Abstract

// Cheng-Rong Xie 1, * , Zhao Li 1, * , Hong-Guang Sun 1, * , Fu-Qiang Wang 1 , Yu Sun 1 , Wen-Xiu Zhao 1 , Sheng Zhang 1 , Wen-Xing Zhao 1 , Xiao-Min Wang 1 , Zhen-Yu Yin 1 1 Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Fujian, P.R. China * These authors have contributed equally to this work Correspondence to: Zhen-Yu Yin, e-mail: yinzy@xmu.edu.cn Keywords: EZH2, CHD5, hepatocellular carcinoma, prognosis, invasion Received: March 02, 2015      Accepted: September 20, 2015      Published: October 26, 2015 ABSTRACT Chromodomain helicase DNA binding protein 5 (CHD5) acts as a tumor suppressor in many cancers. In the present study, we demonstrated that reduced levels of CHD5 in hepatocellular carcinoma (HCC) tissues were significantly associated with metastasis and poor prognosis. Gain-of-function assays revealed that CHD5 suppressed motility and invasion of HCC cells. Subsequent investigations showed that CHD5 was epigenetically silenced by polycomb repressive complex 2 (PRC2)-mediated the trimethylation of histone H3 at lysine 27 (H3K27me3) in HCC cells. Furthermore, overexpression of CHD5 repressed enhancer of zeste homolog 2 (EZH2) and activated PRC2 target genes, such as p16 and p21 . Chromatin immunoprecipitation and luciferase reporter assays also showed that CHD5 and EZH2 bind to each other’s promoters and inhibit transcription. These findings uncovered, for the first time, a mutual suppression regulation between CHD5 and EZH2, which may provide new insights into their potential therapeutic significance for HCC.