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1、中國科學(xué)技術(shù)大學(xué)碩士學(xué)位論文PAX5TargetsTFIIIIRF4toPromoteMultipleMyelomaCellGrowth姓名：張愛金申請(qǐng)學(xué)位級(jí)別：碩士專業(yè)：細(xì)胞生物學(xué)指導(dǎo)教師：肖衛(wèi)華201011ABSTRACTIIIABSTRACTAsamemberofPax(Pairedbox)tranionfactfamilyPAX5istheonlyonewhodistributedinhematopoieticcells.Itd
2、ecidesBcellgrowthdifferentiationbyrepressingBcelllineageinappropriategenessimultaneouslyactivatingBlineagespecificgenes.ThusPAX5canbothrepressesactivatesasubsetofgenestranion.StudieshaveshownthatPAX5ispresentedduringBcel
3、ldevelopmentdifferentiationfromproBtomatureBcellsitsexpressionisshutteddowninterminallydifferentiatedBcells.Multiplemyeloma(MM)isstillanincurablediseasethatisacterizedbybothmatureBcellplasmacellidentities.Constitutiveexp
4、ressionofPAX5hasbeendetectedinbothclinalsamplescelllinesofMMwhichhasbeenimplicatedinpromotingMMgrowth.ToelucidatetherolesmechanismsofPAX5inMMaMMcelllineIM9wasemployedstablytransfectedwiththeplascontainingshRNAspecifictar
5、getingPAX5wasestablished.ByscreeningthepotentialPAX5targetedgeneswediscoveredthatPAX5regulatesTFIIItranionthroughdirectlybindingtoaPAX5bindingsitewithinTFIIIpromotregionpromotesIM9cellgrowth.MeoverIRF4anotherimptantoncog
6、enethatimplicatedinMMwasalsofoundtobeinducedbyPAX5throughtranionalregulationinvolvedinpromotingMMcellgrowth.CombinationofinhibitionofbothPAX5IRF4bysiRNAshowedamaximalinhibityeffectofMMcellgrowth.FurthermeknockdownPAX5lea
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