REVIEWOpenAccessCircularRNAsinCancer:emergingfunctionsinhallmarks,stemness,resistanceandrolesaspotentialbiomarkersMinSu1,2,4†,YuhangXiao2,3†,JunliangMa1,YanyanTang2,BoTian1,YuqinZhang3,XuLi1,ZhiningWu1,DesongYang1,YongZhou1,HuiWang2,QianjinLiao2,4*andWenxiangWang1,2*AbstractCircularRNAs(circRNAs)areaclassofRNAmoleculeswithclosedloopsandhighstability.CircRNAsareabundantlyexpressedineukaryoticorganismsandexhibitbothlocation-andstep-specificity.Inrecentyears,circRNAsareattractingconsiderableresearchattentionattributedtotheirpossiblecontributionstogeneregulationthroughavarietyofactions,includingspongingmicroRNAs,interactingwithRNA-bindingproteins,regulatingtranscriptionandsplicing,andproteintranslation.GrowingevidencehasrevealedthatcircRNAsplaycriticalrolesinthedevelopmentandprogressionofdiseases,especiallyincancers.Withoutdoubt,expandingourunderstandingofcircRNAswillenrichknowledgeofcancerandprovidenewopportunitiesforcancertherapy.Inthisreview,weprovideanoverviewofthecharacteristics,functionsandfunctionalmechanismsofcircRNAs.Inparticular,wesummarizecurrentknowledgeregardingthefunctionsofcircRNAsinthehallmarks,stemness,resistanceofcancer,aswellasthepossibilityofcircRNAsasbiomarkersincancer.Keywords:CircRNAs,Cancer,Function,Hallmarks,Stemness,Resistance,BiomarkerIntroductionCircRNAsareaclassofsingle-strandedclosedcircularRNAmoleculesthatlack5′-3′endsandpoly(A)tails[1].FourdecadeshaveelapsedsincecircularRNAs(cir-cRNAs)werefirstfoundinplant-basedvirusesin1976[2].CircRNAswerelaterfoundineukaryotesasanen-dogenousRNAsplicingproductin1979andinhumansfollowinghepatitisdeltavirusinfectionin1986[3,4].However,circRNAswereinitiallyconsideredasfunc-tionlessbyproductsofaberrantRNAsplicingandthushavenotgarneredsufficientscientificattention.In2012,Salzmanetal.[5]identifiedtheabundanceofcircRNAspeciesinbothnormalandmammaliancellsandrevealedthatmorethan10%ofexpressedgenesareabletoproducecircRNAs.In2013,Hansenetal.[6]andMemczaketal.[7]reportedthatcirculartranscriptsofcerebellardegen...
