REVIEWOpenAccessFunctionsofN6-methyladenosineanditsroleincancerLiuerHe1,2,HuiyuLi1,2,AnqiWu1,YulongPeng1,GuangShu2andGangYin1*AbstractN6-methyladenosine(m6A)ismethylationthatoccursintheN6-positionofadenosine,whichisthemostprevalentinternalmodificationoneukaryoticmRNA.Accumulatingevidencesuggeststhatm6Amodulatesgeneexpression,therebyregulatingcellularprocessesrangingfromcellself-renewal,differentiation,invasionandapoptosis.M6Aisinstalledbym6Amethyltransferases,removedbym6Ademethylasesandrecognizedbyreaderproteins,whichregulateofRNAmetabolismincludingtranslation,splicing,export,degradationandmicroRNAprocessing.Alterationofm6Alevelsparticipatesincancerpathogenesisanddevelopmentviaregulatingexpressionoftumor-relatedgeneslikeBRD4,MYC,SOCS2andEGFR.Inthisreview,weelaborateonrecentadvancesinresearchofm6Aenzymes.Wealsohighlighttheunderlyingmechanismofm6Aincancerpathogenesisandprogression.Finally,wereviewcorrespondingpotentialtargetsincancertherapy.Keywords:N6-methyladenosine,writer,eraser,reader,cancerBackgroundPost-transcriptionalmodificationhasemergedasanim-portantregulatorofavarietyofphysiologicalprocessesanddiseaseprogression,attractingaccumulatingatten-tioninbioscienceresearch.AmongnumerousRNAmodifications,N6-methyladenosine(m6A)isthemostabundantmRNAmodification.Anaverageof1000nu-cleotidesarefoundtocontain1–2m6Aresidues[1,2].MainlyoccurringintheRRACHsequence(whereR=AorG,H=A,C,orU)[3,4],m6Aisenrichednearthestopcodon,3′untranslatedregion(UTR)andlongin-ternalexon[5,6].M6AcanalsobefoundinRNAofbacteriaandviruses[7,8].M6Acanbeinstalledbythemethyltransferasecom-plex(MTC)andremovedbydemethylases[9,10].M6Aalterstargetgeneexpression,thusinfluencingthecorre-spondingcellprocessesandphysiologicalfunction.Inmolecularmechanism,m6AparticipatesinalmostallstepsofRNAmetabolismincludingmRNAtranslation,degradation,splicing,exportandfolding[11,12].Rolesofm6Ainvariouscancershavebeenreportedrecently[87,88,].Inthisreview,wefocusontheup-to-dateprogressinm6Aenzymes.Wedescribefunctionsofm6Ain...
