APC-activatedlongnon-codingRNAinhibitscolorectalcarcinomapathogenesisthroughreducingexosomeproductionFeng-WeiWang,…,Rui-HuaXu,DanXieJClinInvest.2018.https://doi.org/10.1172/JCI122478.Theadenomatouspolyposiscoli(APC)geneplaysapivotalroleinthepathogenesisofcolorectalcarcinoma(CRC),butremainsachallengefordrugdevelopment.Longnon-codingRNAs(lncRNAs)areinvaluableinidentifyingcancerpathologies,andprovidingtherapeuticoptionsforcancerpatients.Here,weidentifiedalncRNA(lncRNA-APC1)activatedbyAPCthroughlncRNAmicroarrayscreening,andexamineditsexpressionamongalargecohortofCRCtissues.AdecreaseinlncRNA-APC1expressionwaspositivelyassociatedwithlymphnodeand/ordistantmetastasis,amoreadvancedclinicalstage,aswellasapoorprognosisofCRCpatients.Additionally,APCcanenhancelncRNA-APC1expressionbysuppressingtheenrichmentofPPARaonthelncRNA-APC1promoter.Furthermore,enforcedlncRNA-APC1expressionwassufficienttoinhibitCRCcellgrowth,metastasisandtumorangiogenesisbysuppressingexosomeproductionthroughdirectlybindingRab5bmRNAandreducingitsstability.Importantly,exosomesderivedfromlncRNA-APC1-silencedCRCcellspromotedangiogenesisbyactivatingtheMAPKpathwayinendothelialcells,andmoreover,exosomalWnt1largelyenhancedCRCcellproliferationandmigrationthroughnon-canonicialWntsignaling.Collectively,lncRNA-APC1isacriticallncRNAregulatedbyAPCinthepathogenesisofCRC.OurfindingssuggestanAPC-regulatedlncRNA-APC1programasanexploitabletherapeuticmaneuverforCRCpatients.ResearchIn-PressPreviewGastroenterologyOncologyFindthelatestversion:http://jci.me/122478/pdf1APC-activatedlongnon-codingRNAinhibitscolorectalcarcinomapathogenesisthroughreducingexosomeproductionFeng-WeiWang1,Chen-HuiCao1,KaiHan1,Yong-XiangZhao2,Mu-YanCai1,Zhi-ChengXiang1,Jia-XingZhang3,Jie-WeiChen1,4,Li-PingZhong2,YongHuang2,Su-FangZhou2,Xiao-HanJin1,Xin-YuanGuan5,Rui-HuaXu1,DanXie1,2,41SunYat-senUniversityCancerCenter;StateKeyLaboratoryofOncologyinSouthChina;CollaborativeInnovationCenterforCancerMedicine,Guangzhou,China,2NationalCenterforInternationalRes...
