Oct4/miR-1246signalingaxisdrivesWnt/β-cateninactivationinlivercancerstemcellsStellaChai1,Kai-YuNg1,ManTong1,EuniceYLau6,TerenceKLee6,KwokWahChan2,Yun-FeiYuan7,Tan-ToCheung3,Siu-TimCheung8,Xiao-QiWang3,NathalieWong9,Chung-MauLo3,5,KwanMan3,5,Xin-YuanGuan4,5,StephanieMa1,51SchoolofBiomedicalSciences,Departmentsof2Pathology,3Surgeryand4ClincialOncology,5StateKeyLaboratoryforLiverResearch,LiKaShingFacultyofMedicine,TheUniversityofHongKong,HongKong;6DepartmentofAppliedBiology&ChemicalTechnology,TheHongKongPolytechnicUniversity,HongKong;7StateKeyLaboratoryofOncologyinSouthernChina,SunYat-SenUniversityCancerCenter,Guangzhou,China;Departmentsof8Surgeryand9AnatomicalandCellularPathology,FacultyofMedicine,TheChineseUniversityofHongKong,HongKongAddressreprintrequeststo:StephanieMa,PhD,SchoolofBiomedicalSciences,LiKaShingFacultyofMedicine,TheUniversityofHongKong,1/F,LaboratoryBlock,21SassoonRoad,PokFuLam,HongKong.E-mail:stefma@hku.hk;Tel:852-3917-9238;Fax:852-2817-0857Shorttitle:Oct-4/miR-1246andβ-catenininHCCstemnessKeywords:tumor-initiatingcells;β-catenin;AXIN2;GSK3β;self-renewal;therapyresistance;Oct4Abbreviations:AFP,alphafetoprotein;AUC,areaundercurve;ChIP,chromatinimmunoprecipitation;CI,confidenceinterval;CSC,cancerstemcell;DIG,digoxigenin;EV,emptyvector;GSK3β,glycogensynthasekinase3β;HCC,hepatocellularcarcinoma;HUVEC,humanumbilicalveinendothelialcell;IHC,immunohistochemistry;IP,input;ISH,insituhybridization;KD,knockdown;lncRNA,longnoncodingRNA;miRNA,microRNA;OE,overexpression;qRT-PCR,quantitativerealtimepolymerasechainreaction;RIP,ribonucleoproteinimmunoprecipitation;RISC,RNA-inducedsilencingcomplex;ROC,receiver-operatingcharacteristic;siC,siControl;WL,wholelysate;ZIP,scramblehairpincontrolAuthorcontributions:SCandSMcameupwiththeconceptofthepaperanddesignedtheexperiments.SCandKYNperformedtheexperimentswithassistancefromMTandEYL.KWCThisarticlehasbeenacceptedforpublicationandundergonefullpeerreviewbuthasnotbeenthroughthecopyediting,typesetting,paginationandproofre...
