ARTICLENon-codingRNAsparticipateintheregulatorynetworkofCLDN4viaceRNAmediatedmiRNAevasionYong-xiSong1,Jing-xuSun1,Jun-huaZhao1,Yu-chongYang1,Jin-xinShi1,Zhong-huaWu1,Xiao-wanChen1,PengGao1,Zhi-fengMiao1,2&Zhen-ningWang1Thousandsofgeneshavebeenwelldemonstratedtoplayimportantrolesincancerprogression.Asgenesdonotfunctioninisolation,theycanbegroupedinto“networks”basedontheirinteractions.Inthisstudy,wediscoveranetworkregulatingClaudin-4ingastriccancer.WeobservethatClaudin-4isup-regulatedingastriccancerandisassociatedwithpoorprognosis.Claudin-4reinforceproliferation,invasion,andEMTinAGS,HGC-27,andSGC-7901cells,whichcouldbereversedbymiR-596andmiR-3620-3p.Inaddition,lncRNA-KRTAP5-AS1andlncRNA-TUBB2AcouldactascompetingendogenousRNAstoaffectthefunctionofClaudin-4.Ourresultssuggestthatnon-codingRNAsplayimportantrolesintheregulatorynetworkofClaudin-4.Assuch,non-codingRNAsshouldbeconsideredaspotentialbiomarkersandtherapeutictargetsagainstgastriccancer.DOI:10.1038/s41467-017-00304-1OPEN1DepartmentofSurgicalOncologyandGeneralSurgery,TheFirstAffiliatedHospitalofChinaMedicalUniversity,155NorthNanjingStreet,HepingDistrict,ShenyangCity110001,China.2DivisionofGastroenterology,DepartmentofMedicine,WashingtonUniversitySchoolofMedicine,StLouis,MO63110,USA.Yong-xiSong,Jing-xuSunandJun-huaZhaocontributedequallytothiswork.CorrespondenceandrequestsformaterialsshouldbeaddressedtoZ.-n.W.(email:josieon826@sina.cn)NATURECOMMUNICATIONS|8:289|DOI:10.1038/s41467-017-00304-1|www.nature.com/naturecommunications1Gastriccancer(GC)isoneofthemostcommoncancers,withaheavymortalityrateallovertheworld1.Metastasis,anendconsequenceofnumerouscomplexprocesses,presentsamajorchallengeinclinicalpracticeandaccountsforamajorsourceofmortalityandrecurrenceinGC2.Duringthecomplexprocessofmetastasis,primarycancercellsundergoasequentialseriesofeventsincludinglocaldissemination,intra-vasationintothevascularsystem,survivalinthecirculatorysystem,extravasationoutofthevascularsystem,andregrowthatdistantsites3–5.Uptonow,man...
