REVIEWOpenAccessRolesofcircRNAsinthetumourmicroenvironmentQiugeZhang2,3,WeiweiWang4,QuanboZhou1,ChenChen1,3,WeitangYuan1,JinboLiu1*,XiaoliLi2*andZhenqiangSun1,3*AbstractThetumourmicroenvironment(TME)constitutestheareasurroundingthetumourduringitsdevelopmentandhasbeendemonstratedtoplayrolesincancer-relateddiseasesthroughcrosstalkwithtumourcells.CircularRNAs(circRNAs)areasubpopulationofendogenousnoncodingRNAs(ncRNAs)thatareubiquitouslyexpressedineukaryotesandhavemultiplebiologicalfunctionsintheregulationofcanceronsetandprogression.AnincreasingnumberofstudieshaveshownthatcircRNAsparticipateinthemultifacetedbiologicalregulationoftheTME.However,detailsonthemechanismsinvolvedhaveremainedelusiveuntilnow.Inthisreview,weanalysetheeffectsofcircRNAsontheTMEfromvariousperspectives,includingimmunesurveillance,angiogenesis,hypoxia,matrixremodelling,exo-circRNAsandchemoradiationresistance.Currently,theenormouspotentialforcircRNAuseintargetedtherapyandasnoninvasivebiomarkershavedrawnourattention.WeemphasizetheprospectoftargetingcircRNAsasanessentialstrategytoregulateTME,overcomecancerresistanceandimprovetherapeuticoutcomes.Keywords:CircRNAs,Tumourmicroenvironment,Immunoregulation,AngiogenesisIntroductionDuringthepastdecadesofcancerresearch,chemo-andradiotherapyhavebeenrecognizedasthemosteffectiveandextensiveapproachesforcancertreatment,buttheirclinicalapplicationsarelimitedduetotheirtoxicsideef-fects[1].Thetumourmicroenvironment(TME)istheproductofthecrosstalkbetweendifferentcelltypes,andplaysacrucialroleintheprogression,metastasisandtherapeutictreatmentofcancer[2–4].Therefore,cancertherapeuticstrategieshavealsograduallyshiftedfromma-lignanttumourcellstotheTMEanditscomplexinterac-tions.Inrecentyears,theTMEhasbeenconsideredaprospectivebreakthroughinmoleculardiagnosisandtreatment,andTMEresearchhasprovidednewideasforcancertherapyandpossiblepreventivestrategies[5,6].CriticalissuesregardingtherolesoftheTMEintumourprogressionandresponsetotreatmentincludeitseffectsonimmunology[7],angio...
