Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma

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 reveale...

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Main Authors:	Xie, Cheng-Rong, Li, Zhao, Sun, Hong-Guang, Wang, Fu-Qiang, Sun, Yu, Zhao, Wen-Xiu, Zhang, Sheng, Zhao, Wen-Xing, Wang, Xiao-Min, Yin, Zhen-Yu
Format:	Online
Language:	English
Published:	Impact Journals LLC 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747380/

id	pubmed-4747380
recordtype	oai_dc
spelling	pubmed-47473802016-03-24 Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma Xie, Cheng-Rong Li, Zhao Sun, Hong-Guang Wang, Fu-Qiang Sun, Yu Zhao, Wen-Xiu Zhang, Sheng Zhao, Wen-Xing Wang, Xiao-Min Yin, Zhen-Yu Research Paper 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. Impact Journals LLC 2015-10-26 /pmc/articles/PMC4747380/ /pubmed/26517514 Text en Copyright: © 2015 Xie et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Xie, Cheng-Rong Li, Zhao Sun, Hong-Guang Wang, Fu-Qiang Sun, Yu Zhao, Wen-Xiu Zhang, Sheng Zhao, Wen-Xing Wang, Xiao-Min Yin, Zhen-Yu
spellingShingle	Xie, Cheng-Rong Li, Zhao Sun, Hong-Guang Wang, Fu-Qiang Sun, Yu Zhao, Wen-Xiu Zhang, Sheng Zhao, Wen-Xing Wang, Xiao-Min Yin, Zhen-Yu Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma
author_facet	Xie, Cheng-Rong Li, Zhao Sun, Hong-Guang Wang, Fu-Qiang Sun, Yu Zhao, Wen-Xiu Zhang, Sheng Zhao, Wen-Xing Wang, Xiao-Min Yin, Zhen-Yu
author_sort	Xie, Cheng-Rong
title	Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma
title_short	Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma
title_full	Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma
title_fullStr	Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma
title_full_unstemmed	Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma
title_sort	mutual regulation between chd5 and ezh2 in hepatocellular carcinoma
description	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.
publisher	Impact Journals LLC
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747380/
_version_	1613536212473085952

Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma

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