资源描述：
《MicroRNA-155 is regulated by the transforming growth factor beta-Smad pathway and contributes to epithelial cell plasticity by targeting RhoA》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
1、MOLECULARANDCELLULARBIOLOGY,Nov.2008,p.67736784Vol.28,No.220270-7306/08/$08.000doi:10.1128/MCB.00941-08Copyright©2008,AmericanSocietyforMicrobiology.AllRightsReserved.MicroRNA-155IsRegulatedbytheTransformingGrowthFactor/SmadPathwayandContributestoEpithelialCell
2、PlasticitybyTargetingRhoA1,21113WilliamKong,HuaYang,LiliHe,Jian-junZhao,DomenicoCoppola,41WilliamS.Dalton,andJinQ.Cheng*134DepartmentsofMolecularOncology,Pathology,andExperimentalTherapeutics,H.LeeMoffittCancerCenterandResearchInstitute,Tampa,Florida33612,andDepa
3、rtmentofPathologyandCellBiology,CollegeofMedicine,2UniversityofSouthFlorida,Tampa,Florida33612Received12June2008/Returnedformodification1August2008/Accepted8September2008Transforminggrowthfactor(TGF-)signalingfacilitatesmetastasisinadvancedmalignancy.Whileanumbe
4、rofprotein-encodinggenesareknowntobeinvolvedinthisprocess,informationontheroleofmicroRNAs(miRNAs)inTGF--inducedcellmigrationandinvasionisstilllimited.Byhybridizinga515-miRNAoligonucleotide-basedmicroarraylibrary,atotalof28miRNAswerefoundtobesignificantlydereg-ula
5、tedinTGF--treatednormalmurinemammarygland(NMuMG)epithelialcellsbutnotSmad4knockdownNMuMGcells.AmongupregulatedmiRNAs,miR-155wasthemostsignificantlyelevatedmiRNA.TGF-inducesmiR-155expressionandpromoteractivitythroughSmad4.TheknockdownofmiR-155suppressedTGF--indu
6、cedepithelial-mesenchymaltransition(EMT)andtightjunctiondissolution,aswellascellmigrationandinvasion.Further,theectopicexpressionofmiR-155reducedRhoAproteinanddisruptedtightjunctionformation.ReintroducingRhoAcDNAwithoutthe3untranslatedregionlargelyreversedthephe
7、-notypeinducedbymiR-155andTGF-.Inaddition,elevatedlevelsofmiR-155werefrequentlydetectedininvasivebreastcancertissues.ThesedatasuggestthatmiR-155mayplayanimportantroleinTGF--inducedEMTandcellmigrationandinvasionbytargetingRhoAandindicatethatitisapotentialtherape
8、utictargetforbreastcancerintervention.MetastasisaccountsforthemajorityofdeathsofcancerSmad-bindingelementsandassociateswithaplethoraoftran-patients,andthus,iti
