REVIEWOpenAccessNovelinsightsintotheinterplaybetweenm6AmodificationandnoncodingRNAsincancerYou-CaiYi,Xiao-YuChen,JingZhang*andJin-ShuiZhu*AbstractN6-methyladenosine(m6A)isoneofthemostcommonRNAmodificationsineukaryotes,mainlyinmessengerRNA(mRNA).Increasingevidenceshowsthatm6Amethylationmodificationactsanessentialroleinvariousphysiologicalandpathologicalbioprocesses.NoncodingRNAs(ncRNAs),includingmiRNAs,lncRNAsandcircRNAs,areknowntoparticipateinregulatingcelldifferentiation,angiogenesis,immuneresponse,inflammatoryresponseandcarcinogenesis.m6Aregulators,suchasMETTL3,ALKBH5andIGF2BP1havebeenreportedtoexecuteam6A-dependentmodificationofncRNAsinvolvedincarcinogenesis.Meanwhile,ncRNAscantargetormodulatem6Aregulatorstoinfluencecancerdevelopment.Inthisreview,weprovideaninsightintotheinterplaybetweenm6AmodificationandncRNAsincancer.Keywords:NoncodingRNAs,Cancer,m6ARNAmethylationIntroductionUptonow,morethan100kindsofRNAmodificationshavebeenconfirmed[1].Amongthem,m6ARNAmethylationisoneofthemostthoroughlystudiedmodi-fications.m6ARNAmodificationoccursbymethylationofthesixthNatomofadenine(A)inmRNAsorncRNAs[2].m6Amodificationsitestendtobefoundinthestopcodonsand3′-Untranslatedregion(3′-UTR)ofmRNAwithatypicalconsensussequenceRRACH(R=GorAandH=A,C,orU)[3,4].Accumulatingdatashowthatm6ARNAmethylationactsbymodulatingcircadianrhythm,geneexpression,celldifferentiation,stressresponse,inflammatoryresponse,andcarcinogen-esis[5–10].Accordingtotheglobalcancerstatistics,therewereestimated18.1millionnewcasesand9.6mil-liondeathsin2018[11].Recentstudieshaveshownthatm6Amodificationactsavitalroleinthediagnosis,treatmentandprognosisofcancerpatientsaswellasincarcinogenesis.Italsoregulatesflysex,virusgenome,meiosisofyeast,tissuedifferentiation,germination,andcollateralgenerationofArabidopsis[12–15].NoncodingRNAs(ncRNAs)includingmicroRNAs(miRNAs),longnon-codingRNAs(lncRNAs)andcircu-larRNAs(circRNAs)actpivotalrolesincancer[16–18].m6AmodificationcanaffectncRNAsplicingandmatur-ationinvolvedincarcinog...
