Oncogenehttps://doi.org/10.1038/s41388-018-0614-4ARTICLELongnoncodingRNACRCMSLsuppressestumorinvasiveandmetastasisincolorectalcarcinomathroughnucleocytoplasmicshuttlingofHMGB2QinruiHan1●LijunXu2,3●WeihaoLin3,4●XueqingYao5●MuhongJiang3,6●RuiZhou3,6●XuegangSun1●LiangZhao2,3,6Received:21May2018/Accepted:29October2018©SpringerNatureLimited2018AbstractLongnoncodingRNAs(lncRNAs)arepervasivetranscriptsthatplaypivotalrolesinregulatingchromatindynamics,geneandproteinexpression.AberrantexpressionandmutationsoflncRNAsrepresentadrivingforcebehindtumorinvasionandmetastasis,makingthemattractivecancertargets.However,mostofthelncRNAsarestillbeingdiscoveredandconclusiveexperimentalevidencefortheirfunctionalrelevanceisstilllackingformostmalignancies.Inthisstudy,adifferentiallyexpressedlncRNA,designatedaslnc-CRCMSL,isidentifiedbymicroarray-basedscreeningsonnon-metastaticandmetastaticCRCspecimens.Lnc-CRCMSLisverifiedasananti-metastaticgeneandnegativelycorrelatedwiththepoorprognosisofCRCpatients.Lnc-CRCMSLoverexpressionrestrictstumorgrowthandmetastasisinvivoandinvitro.Instead,lnc-CRCMSLsilencingacceleratesCRCcellproliferationandmigration.RNA-pulldownassayidentifieshighmobilitygroupbox2(HMGB2)asadownstreamproteinoflnc-CRCMSL.Mechanically,lnc-CRCMSLphysicallybindstoHMGB2andstabilizesthelocalizationofHMGB2inthecytoplasm.Notably,lnc-CRCMSLknockdownleadtotheshiftofHMGB2intonuclear,inwhichittriggersepithelialtomesenchymaltransition(EMT)programming.Importantly,lnc-CRCMSLcontrolsthecytoplasmicretentionofHMGB2andattenuatestheinteractionbetweenHMGB2andOCT4tosuppressEMT.TreatmentofleptomycinB(LMB),apotentandspecificnuclearexportinhibitor,counteractslnc-CRCMSL-mediatedsuppressionofaggressivephenotypesandEMTprocessbyaccumulatingthenuclearHMGB2.ConclusionOurdatahighlighttheanti-metastaticroleoflnc-CRCMSLinstabilizingHMGB2throughlncRNA-proteininteractionsinthecytoplasm,andsuggestthattargetinglnc-CRCMSLmayrepresentatherapeuticopportunityformanagingmetastaticCRC.IntroductionLongnoncodingRNAs(...
