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1、BiochimicaetBiophysicaActa1843(2014)1834–1838ContentslistsavailableatScienceDirectBiochimicaetBiophysicaActajournalhomepage:www.elsevier.com/locate/bbamcrRANKLexpressioninmyelomacellsisregulatedbyanetworkinvolvingRANKLpromotermethylation,DNMT1,microRNAandTNFαinthemicroenvironmentLingqingYuan,G
2、odfreyChiFungChan,KwongLamFung,ChorSangChim⁎DepartmentofMedicine,QueenMaryHospital,UniversityofHongKong,HongKong,ChinaDepartmentofPaediatricsandAdolescentMedicine,FacultyofMedicine,TheUniversityofHongKong,HongKong,ChinaarticleinfoabstractArticlehistory:WestudiedtheregulationofRANKLexpressionin
3、myelomabypromoterDNAmethylation.Methylation-specificReceived11November2013polymerasechainreactionshowedcompletemethylationofRANKLpromoterinWL-2myelomacellsbutpartialReceivedinrevisedform8May2014methylationineightotherlines.5-AzadCtreatmentofWL-2cellsledtodemethylationandre-expressionofAccepted1
4、9May2014RANKL.Transwellandcontactco-cultureofWL-2cellswithnormalbonemarrow-derivedmesenchymalstromalAvailableonline26May2014cells(BMSCs)resultedincomparablerepressionofDNAmethyltransferase-1(DNMT1)andre-expressionofRANKLinWL-2cells.Moreover,treatmentofWL-2cellswithTNFαledtorepressionofDNMT1and
5、re-Keywords:RANKLexpressionofRANKLinassociationwithupregulationofmiR-140-3pandmiR-126,whicharepartiallyoffsetMyelomamicroenvironmentbyadditionofanti-TNFαantibodytotranswell-cocultureofWL2withBMSC.Takentogether,ourresultsshowedDNAmethylationthatTNFαinthemarrowmicroenvironmentledtoRANKLdemethyla
6、tionandre-expressioninmyelomacellsDNMT1throughDNMT1repressionandupregulationofmiR-126-3pandmiR-140,bothknowntorepressDNMT1MicroRNAtranslation.TNFα©2014ElsevierB.V.Allrightsreserved.1.IntroductionInMM,theBMmicroenvironmentplaysanessentialroleinmyelo-maplasmacellproliferation,migration,survivala
7、nddrugresistanceMultiplemyeloma(MM)ischaracterizedbyclonalproliferationof[8].Moreover,ithasbeensuggestedthattheBMmicroenvironmentmalignantplasmacellsinthebonemarrow,associatedwithosteolyticstimulatedRANKLexpressionfromBMSCswhenco-cultur
