Hepatitis C virus core protein interacts with zinc finger E-box binding homeobox 2 to inhibit E-cadherin expression

Objective To investigate the molecular mechanism by which hepatitis C virus (HCV) core protein represses the expression of E-cadherin by interacting with zinc finger E-box binding homeobox 2 (ZEB2). Methods A HepG2 cell line stably expressing HCV core protein was constructed by transfecting the cell...

Full description

Bibliographic Details
Main Authors: LIU Chuanli, MAO Jinju, YE Yuanyuan, HU Qin, ZHANG Lijun, CHEN Weixian
Format: Article
Language:zho
Published: Editorial Office of Journal of Third Military Medical University 2019-09-01
Series:Di-san junyi daxue xuebao
Subjects:
Online Access:http://aammt.tmmu.edu.cn/Upload/rhtml/201904168.htm
_version_ 1818863213881589760
author LIU Chuanli
MAO Jinju
YE Yuanyuan
HU Qin
ZHANG Lijun
CHEN Weixian
author_facet LIU Chuanli
MAO Jinju
YE Yuanyuan
HU Qin
ZHANG Lijun
CHEN Weixian
author_sort LIU Chuanli
collection DOAJ
description Objective To investigate the molecular mechanism by which hepatitis C virus (HCV) core protein represses the expression of E-cadherin by interacting with zinc finger E-box binding homeobox 2 (ZEB2). Methods A HepG2 cell line stably expressing HCV core protein was constructed by transfecting the cells with pCore-3FLAG and G418 screening. The expression levels of ZEB2 and E-cadherin in the transfected cells were examined with RT-PCR and Western blotting, and the promoter activity of E-cadherin was assayed using a dual luciferase system. The interaction of HCV core protein with ZEB2 was detected by immunoprecipitation, and the binding of ZEB2 with E-cadherin promoter was determined by chromatin immuoprecipitation. Results Compared with the control cells, the cells transiently and stably expressing HCV core protein both showed significantly decreased expression of E-cadherin (P < 0.01) and increased ZEB2 expression (P < 0.05) at both the protein and mRNA levels. HepG2 cells transfected with HCV core protein exhibited obviously lowered luciferase activity driven by E-cadherin promoter (P < 0.01), while ZEB2 knockdown by RNA interference partly recovered the luciferase activity (P < 0.05). Immunoprecipitation results demonstrated that HCV core protein could bind directly to ZEB2. Chromatin immunoprecipitation assay showed that the presence of HCV core protein obviously enhanced the binding of ZEB2 to E-cadherin promoter. Conclusion HCV core protein increases the expression of ZEB2 and enhances its binding to E-cadherin promoter, and thus inhibits the expression of E-cadherin.
first_indexed 2024-12-19T10:12:12Z
format Article
id doaj.art-752c11cb46684119888ca1d1b0e73a18
institution Directory Open Access Journal
issn 1000-5404
language zho
last_indexed 2024-12-19T10:12:12Z
publishDate 2019-09-01
publisher Editorial Office of Journal of Third Military Medical University
record_format Article
series Di-san junyi daxue xuebao
spelling doaj.art-752c11cb46684119888ca1d1b0e73a182022-12-21T20:26:20ZzhoEditorial Office of Journal of Third Military Medical UniversityDi-san junyi daxue xuebao1000-54042019-09-0141181744174910.16016/j.1000-5404.201904168Hepatitis C virus core protein interacts with zinc finger E-box binding homeobox 2 to inhibit E-cadherin expressionLIU Chuanli0MAO Jinju1YE Yuanyuan2HU Qin3ZHANG Lijun4CHEN Weixian5Department of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, ChinaDepartment of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, ChinaDepartment of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, ChinaDepartment of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, ChinaDepartment of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, ChinaDepartment of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, ChinaObjective To investigate the molecular mechanism by which hepatitis C virus (HCV) core protein represses the expression of E-cadherin by interacting with zinc finger E-box binding homeobox 2 (ZEB2). Methods A HepG2 cell line stably expressing HCV core protein was constructed by transfecting the cells with pCore-3FLAG and G418 screening. The expression levels of ZEB2 and E-cadherin in the transfected cells were examined with RT-PCR and Western blotting, and the promoter activity of E-cadherin was assayed using a dual luciferase system. The interaction of HCV core protein with ZEB2 was detected by immunoprecipitation, and the binding of ZEB2 with E-cadherin promoter was determined by chromatin immuoprecipitation. Results Compared with the control cells, the cells transiently and stably expressing HCV core protein both showed significantly decreased expression of E-cadherin (P < 0.01) and increased ZEB2 expression (P < 0.05) at both the protein and mRNA levels. HepG2 cells transfected with HCV core protein exhibited obviously lowered luciferase activity driven by E-cadherin promoter (P < 0.01), while ZEB2 knockdown by RNA interference partly recovered the luciferase activity (P < 0.05). Immunoprecipitation results demonstrated that HCV core protein could bind directly to ZEB2. Chromatin immunoprecipitation assay showed that the presence of HCV core protein obviously enhanced the binding of ZEB2 to E-cadherin promoter. Conclusion HCV core protein increases the expression of ZEB2 and enhances its binding to E-cadherin promoter, and thus inhibits the expression of E-cadherin.http://aammt.tmmu.edu.cn/Upload/rhtml/201904168.htmhepatitis c viruscore proteinhepatocellular carcinoma
spellingShingle LIU Chuanli
MAO Jinju
YE Yuanyuan
HU Qin
ZHANG Lijun
CHEN Weixian
Hepatitis C virus core protein interacts with zinc finger E-box binding homeobox 2 to inhibit E-cadherin expression
Di-san junyi daxue xuebao
hepatitis c virus
core protein
hepatocellular carcinoma
title Hepatitis C virus core protein interacts with zinc finger E-box binding homeobox 2 to inhibit E-cadherin expression
title_full Hepatitis C virus core protein interacts with zinc finger E-box binding homeobox 2 to inhibit E-cadherin expression
title_fullStr Hepatitis C virus core protein interacts with zinc finger E-box binding homeobox 2 to inhibit E-cadherin expression
title_full_unstemmed Hepatitis C virus core protein interacts with zinc finger E-box binding homeobox 2 to inhibit E-cadherin expression
title_short Hepatitis C virus core protein interacts with zinc finger E-box binding homeobox 2 to inhibit E-cadherin expression
title_sort hepatitis c virus core protein interacts with zinc finger e box binding homeobox 2 to inhibit e cadherin expression
topic hepatitis c virus
core protein
hepatocellular carcinoma
url http://aammt.tmmu.edu.cn/Upload/rhtml/201904168.htm
work_keys_str_mv AT liuchuanli hepatitiscviruscoreproteininteractswithzincfingereboxbindinghomeobox2toinhibitecadherinexpression
AT maojinju hepatitiscviruscoreproteininteractswithzincfingereboxbindinghomeobox2toinhibitecadherinexpression
AT yeyuanyuan hepatitiscviruscoreproteininteractswithzincfingereboxbindinghomeobox2toinhibitecadherinexpression
AT huqin hepatitiscviruscoreproteininteractswithzincfingereboxbindinghomeobox2toinhibitecadherinexpression
AT zhanglijun hepatitiscviruscoreproteininteractswithzincfingereboxbindinghomeobox2toinhibitecadherinexpression
AT chenweixian hepatitiscviruscoreproteininteractswithzincfingereboxbindinghomeobox2toinhibitecadherinexpression