Enhancement of Canonical Wntβ-Catenin Signaling Activity by HCV Core Protein Promotes Cell Growth of Hepatocellular Carcinoma Cells 英文参考文献.docVIP

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Enhancement of Canonical Wntβ-Catenin Signaling Activity by HCV Core Protein Promotes Cell Growth of Hepatocellular Carcinoma Cells 英文参考文献.doc

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Enhancement of Canonical Wntβ-Catenin Signaling Activity by HCV Core Protein Promotes Cell Growth of Hepatocellular Carcinoma Cells 英文参考文献

EnhancementofCanonicalWnt/b-CateninSignaling ActivitybyHCVCoreProteinPromotesCellGrowthof HepatocellularCarcinomaCells JiaoLiu1.,XiongDing1.,JiaTang1.,YoudeCao2,PengHu1,FanZhou1,XiaoliangShan1,XuefeiCai1, QingmeiChen1,NingLing1,BingqiangZhang3,YangBi4,KeChen1,HongRen1,AilongHuang1 ,Tong- ChuanHe4,5,NiTang1* 1TheSecondAffiliatedHospitalandtheKeyLaboratoryofMolecularBiologyofInfectiousDiseasesdesignatedbytheChineseMinistryofEducation,ChongqingMedical University,Chongqing,China,2DepartmentofPathology,ChongqingMedicalUniversity,Chongqing,China,3TheFirstAffiliatedHospital,ChongqingMedicalUniversity, Chongqing, China, 4Stem Cell Biology and Therapy Laboratory, The Children’s Hospital, Chongqing Medical University, Chongqing, China, 5Molecular Oncology Laboratory,DepartmentofSurgery,TheUniversityofChicagoMedicalCenter,Chicago,Illinois,UnitedStatesofAmerica Abstract Background:TheHepatitisCvirus(HCV)coreproteinhasbeenimplicatedasapotentialoncogeneoracofactorinHCV- relatedhepatocellularcarcinoma(HCC),buttheunderlyingmechanismsareunknown.OveractivationoftheWnt/b-catenin signaling is a major factor in oncogenesis of HCC. However, the pathogenesis of HCV core-associated Wnt/b-catenin activationremainstobefurthercharacterized.Therefore,weattemptedtodeterminewhetherHCVcoreproteinplaysan importantroleinregulatingWnt/b-cateninsignalinginHCCcells. Methodology: Wnt/b-catenin signaling activity was investigated in core-expressing hepatoma cells. Protein and gene expressionwereexaminedbyWesternblot,immunofluorescencestaining,RT-qPCR,andreporterassay. Principal Findings: HCV core protein significantly enhances Tcf-dependent transcriptional activity induced by Wnt3A in HCC cell lines. Additionally, core protein increases and stabilizes b-catenin levels in hepatoma cell line Huh7 through inactivationofGSK-3b,whichcontributestotheup-regulationofdownstreamtargetgenes,suchasc-Myc,cyclinD1,WISP2 andCTGF.Also,coreproteinincreasescellproliferationrateandpromotesWnt3A-inducedtumorgrowthinthexe