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Article: Epigenetic repression of E-cadherin expression by Hepatitis B virus x Antigen (HBx) in liver cancer

TitleEpigenetic repression of E-cadherin expression by Hepatitis B virus x Antigen (HBx) in liver cancer
Authors
Issue Date2012
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2012, v. 31 n. 5, p. 563-572 How to Cite?
AbstractLoss of E-cadherin is associated with acquisition of metastatic capacity. Numerous studies suggest that histone deacetylation and/or hypermethylation of CpG islands in E-cadherin gene (CDH1) are major mechanisms responsible for E-cadherin silencing in different tumors and cancer cell lines. The hepatitis B virus (HBV)-encoded X antigen, HBx, contributes importantly to the development of hepatocellular carcinoma using multiple mechanisms. Experiments were designed to test if in addition to CDH1 hypermethylation HBx promotes epigenetic modulation of E-cadherin transcriptional activity through histone deacetylation and miR-373. The relationships between HBx, E-cadherin, mSin3A, Snail-1 and miR-373 were evaluated in HBx expressing (HepG2X) and control (HepG2CAT) cells by western blotting, immunoprecipitation (IP), chromatin IP as well as by immunohistochemical staining of liver and tumor tissue sections from HBV-infected patients. In HepG2X cells, decreased levels of E-cadherin and elevated levels of mSin3A and Snail-1 were detected. Reciprocal IP with anti-HBx and anti-mSin3A demonstrated mutual binding. Furthermore, HBx-mSin3A colocalization was detected by immunofluorescent staining. HBx downregulated E-cadherin expression by the recruitment of the mSin3A/histone deacetylase complex to the Snail-binding sites in human CDH1. Histone deacetylation inhibition by Trichostatin-A treatment restored E-cadherin expression. Mir-373, a positive regulator of E-cadherin expression, was downregulated by HBx in HepG2X cells and tissue sections from HBV-infected patients. Thus, histone deacetylation of CDH1 and downregulation of miR-373, together with the previously demonstrated hypermethylation of CDH1 by HBx, may be important for the understanding of HBV-related carcinogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/160067
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorArzumanyan, Aen_US
dc.contributor.authorFriedman, Ten_US
dc.contributor.authorKotei, Een_US
dc.contributor.authorNg, IOLen_US
dc.contributor.authorLian, Zen_US
dc.contributor.authorFeitelson, MAen_US
dc.date.accessioned2012-08-16T06:02:15Z-
dc.date.available2012-08-16T06:02:15Z-
dc.date.issued2012en_US
dc.identifier.citationOncogene, 2012, v. 31 n. 5, p. 563-572en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttp://hdl.handle.net/10722/160067-
dc.description.abstractLoss of E-cadherin is associated with acquisition of metastatic capacity. Numerous studies suggest that histone deacetylation and/or hypermethylation of CpG islands in E-cadherin gene (CDH1) are major mechanisms responsible for E-cadherin silencing in different tumors and cancer cell lines. The hepatitis B virus (HBV)-encoded X antigen, HBx, contributes importantly to the development of hepatocellular carcinoma using multiple mechanisms. Experiments were designed to test if in addition to CDH1 hypermethylation HBx promotes epigenetic modulation of E-cadherin transcriptional activity through histone deacetylation and miR-373. The relationships between HBx, E-cadherin, mSin3A, Snail-1 and miR-373 were evaluated in HBx expressing (HepG2X) and control (HepG2CAT) cells by western blotting, immunoprecipitation (IP), chromatin IP as well as by immunohistochemical staining of liver and tumor tissue sections from HBV-infected patients. In HepG2X cells, decreased levels of E-cadherin and elevated levels of mSin3A and Snail-1 were detected. Reciprocal IP with anti-HBx and anti-mSin3A demonstrated mutual binding. Furthermore, HBx-mSin3A colocalization was detected by immunofluorescent staining. HBx downregulated E-cadherin expression by the recruitment of the mSin3A/histone deacetylase complex to the Snail-binding sites in human CDH1. Histone deacetylation inhibition by Trichostatin-A treatment restored E-cadherin expression. Mir-373, a positive regulator of E-cadherin expression, was downregulated by HBx in HepG2X cells and tissue sections from HBV-infected patients. Thus, histone deacetylation of CDH1 and downregulation of miR-373, together with the previously demonstrated hypermethylation of CDH1 by HBx, may be important for the understanding of HBV-related carcinogenesis.-
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc-
dc.relation.ispartofOncogeneen_US
dc.subject.meshBlotting, Western-
dc.subject.meshCadherins - genetics - metabolism-
dc.subject.meshDNA Methylation-
dc.subject.meshLiver Neoplasms - genetics - metabolism - pathology-
dc.subject.meshTrans-Activators - genetics - metabolism-
dc.titleEpigenetic repression of E-cadherin expression by Hepatitis B virus x Antigen (HBx) in liver canceren_US
dc.typeArticleen_US
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1476-5594 (Electronic) 0950-9232 (Linkin&volume=31&issue=5&spage=563&epage=72&date=2012&atitle=Epigenetic+repression+of+E-cadherin+expression+by+hepatitis+B+virus+x+antigen+in+liver+canceren_US
dc.identifier.emailArzumanyan, A: alla.arzumanyan@temple.eduen_US
dc.identifier.emailNg, IOL: iolng@hku.hk-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1038/onc.2011.255-
dc.identifier.pmid21706058-
dc.identifier.pmcidPMC3183380-
dc.identifier.scopuseid_2-s2.0-84856528807-
dc.identifier.hkuros205483en_US
dc.identifier.volume31en_US
dc.identifier.issue5en_US
dc.identifier.spage563en_US
dc.identifier.epage572en_US
dc.identifier.isiWOS:000300221800003-
dc.publisher.placeUnited Kingdom-
dc.identifier.citeulike9506100-

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