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1、4EpigeneticsandmiRNAsinHumanCancer†MullerFabbri*andGeorgeA.Calin*DepartmentofMolecularVirology,Immunology,andMedicalGeneticsandComprehensiveCancerCenter,OhioStateUniversity,BiomedicalResearchTower,Columbus,Ohio,USADepartmentofExperimentalTherapeuticsandCancerGenetics,UniversityofTexas
2、,M.D.AndersonCancerCenter,Houston,Texas,USAI.IntroductionII.miRNAsasTargetsofEpigeneticChangesinCancerA.EpigeneticscanregulatemiRNAexpressioninmetastatictumorsIII.epi-miRNAs:RegulatorsoftheEpigeneticMachineryIV.ConclusionAcknowledgmentsReferencesABSTRACTEpigeneticfactorsandmicroRNAs(m
3、iRNAs)areregulatorsofgeneexpression.Theirregulatoryfunctionisfrequentlyaberrantincancer.Inthischapter,weshowthatatightconnectionoccursbetweenmiRNAsandepigenetics.Epige-neticfactorscanberesponsiblefortheaberranciesofthemiRNome(definedasthefullspectrumofmiRNAsforaspecificgenome)observedin
4、cancer.Indeed,miRNAsundergothesameepigeneticregulatorylawslikeanyotherprotein-codinggene.Moreover,aspecificgroupofmiRNAs(definedasepi-miRNAs)candirectlytargeteffectorsoftheepigeneticmachinery(suchasDNAmethyl-transferases,histonedeacetylases,andpolycombrepressivecomplexgenes)andAdvancesi
5、nGenetics,Vol.700065-2660/10$35.00Copyright2010,ElsevierInc.Allrightsreserved.DOI:10.1016/S0065-2660(10)70004-388FabbriandCalinindirectlyaffecttheexpressionoftumorsuppressorgenes,whoseexpressioniscontrolledbyepigeneticfactors.TheresultofthisepigeneticmiRNAinterac-tionisanewlayerofcomp
6、lexityingeneregulation,whosecomprehensionopensnewavenuestounderstandhumancancerogenesisandtoachievenewcancertreatments.ß2010,ElsevierInc.I.INTRODUCTIONEpigeneticsisdefinedasallheritablechangesingeneexpressionnotassociatedwithconcomitantalterationsintheDNAsequence.Geneepigeneticregulati
7、onusuallyincludesDNAmethylationandhistonemodifications.DNAmethylationisareversibleprocess,whichoccursinspecificgenomicareascalledCpGislands(HermanandBaylin,2003;Weberetal.,2007),andiscatalyzedbythreemajorDNAmethyltransferases:DNMT1(main-tenanceDNMT),whichpreservesthemethylationpatternst
8、hroug
