1DownregulationofDNMT3AbymiR-708-5pinhibitslungcancerstemcell-likephenotypesthroughrepressingWnt/β-cateninsignalingTianchiLiu1$,XiaopingWu1$,TongChen1,ZeweiLuo1,2,XiaohuaHu1*1.StateKeyLaboratoryofGeneticEngineering,SchoolofLifeSciences,FudanUniversity,Shanghai200433,China2.SchoolofBiosciences,UniversityofBirmingham,EdgbastonBirminghamB152TTUKRunningTitle:miR-708-5pinhibitslungcancerstemnessKeywords:lungcancer,cancerstemcell,miR-708-5p,DNMT3A,Wnt/β-cateninsignaling$:T.LiuandX.Wucontributedequallytothiswork.*:ThecorrespondenceshouldbeaddressedtoDr.XiaohuaHuSchoolofLifeSciencesFudanUniversityShanghai200433,Chinaxhhu@fudan.edu.cnTel:+862151630720Fax:+862151630720Research.onSeptember29,2017.©2017AmericanAssociationforCancerclincancerres.aacrjournals.orgDownloadedfromAuthormanuscriptshavebeenpeerreviewedandacceptedforpublicationbuthavenotyetbeenedited.AuthorManuscriptPublishedOnlineFirstonSeptember28,2017;DOI:10.1158/1078-0432.CCR-17-11692TranslationalrelevanceLungcancerremainstheleadingcauseofcancerdeath.Cancerstemcell(CSC)candrivecancerdevelopment,recurrenceandtherapyresistance.UnderstandinglungCSCsphysiopathologyshouldprovideopportunitytopreventtumordevelopmentandimprovetheirtherapeuticmanagement.MiRNAsrepresentanemergingclassoftargetbiomoleculesconsideredasanalternativetherapeuticapproachindifferenttypesofcancers.Inthisstudy,weidentifiedforthefirsttime,thatmiR-708-5peffectivelysuppressedthecellstemnessoflungcancerbytargetingDNMT3AandthenreducingthesubsequentDNAmethylation.MiR-708-5pwasalsodemonstratedtoactasanovelpromisingprognosticanddiagnosticbiomarkerinNSCLC.Consequently,ourfindingofmiR-708-5p-DNMT3AaxisprovidedinsightsintopathologicmechanismsunderlyingNSCLCstemness,implyingitsclinicalsignificanceindevelopingtargetsforNSCLCpredictionandtherapy.AbstractPurpose:Lungcanceristheleadingcauseofcancerdeathintheworld,andemergingevidencessuggestthatlungcancerstemcells(CSCs)areassociatedwithitspoorprognosis,tumorrecurrenceandtherapyresistance.Herewerevealanovelroleform...
