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...
Main Authors: | , , , , , |
---|---|
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 |