Research Papers:

Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma

Cheng-Rong Xie _, Zhao Li, Hong-Guang Sun, Fu-Qiang Wang, Yu Sun, Wen-Xiu Zhao, Sheng Zhang, Wen-Xing Zhao, Xiao-Min Wang and Zhen-Yu Yin

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Oncotarget. 2015; 6:40940-40952. https://doi.org/10.18632/oncotarget.5724

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Cheng-Rong Xie1,*, Zhao Li1,*, Hong-Guang Sun1,*, Fu-Qiang Wang1, Yu Sun1, Wen-Xiu Zhao1, Sheng Zhang1, Wen-Xing Zhao1, Xiao-Min Wang1, Zhen-Yu Yin1

1Department 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: [email protected]

Keywords: EZH2, CHD5, hepatocellular carcinoma, prognosis, invasion

Received: March 02, 2015     Accepted: September 20, 2015     Published: October 26, 2015


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.

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