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Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3

Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3

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时间：2019-07-09

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1、JournalofPathologyJPathol2011;225:232–242ORIGINALPAPERPublishedonline27June2011inWileyOnlineLibrary(wileyonlinelibrary.com)DOI:10.1002/path.2931DeregulatedmiR-155promotesFas-mediatedapoptosisinhumanintervertebraldiscdegenerationbytargetingFADDandcaspase-3Hai-QiangWang,1†Xiao-DongYu,1†Zhi-HengLiu,

2、1†XinCheng,2DinoSamartzis,3Lin-TaoJia,2Sheng-XiWu,4JingHuang,4JingChen4andZhuo-JingLuo1*1InstituteofOrthopaedics,XijingHospital,FourthMilitaryMedicalUniversity,Xian,PeoplesRepublicofChina2DepartmentofBiochemistryandMolecularBiology,FourthMilitaryMedicalUniversity,Xian,PeoplesRepublicofChina3Depar

3、tmentofOrthopaedicsandTraumatology,UniversityofHongKong,Pokfulam,HongKong,SARChina4DepartmentofAnatomyandK.K.LeungBrainResearchCentre,FourthMilitaryMedicalUniversity,Xian,PeoplesRepublicofChina*Correspondenceto:Zhuo-JingLuo,InstituteofOrthopaedics,XijingHospital,15ChangleWesternRoad,FourthMilitar

4、yMedicalUniversity,Xian710032,PeoplesRepublicofChina.e-mail:zjluo@fmmu.edu.cn†Theseauthorscontributedequallytothisstudy.AbstractTheroleofapoptosisinthepathogenesisofintervertebraldiscdegeneration(IDD)remainsenigmatic.AccumulatingevidencehasshownthattheapoptoticmachineryisregulatedbymiRNAs.Wehypot

5、hesizedthatmiRNAsmightcontributetoapoptosisinIDD.Wehavefoundthat29miRNAsweredifferentiallyexpressedandmiR-155wasdown-regulatedindegenerativenucleuspulposus(NP).ThederegulationofmiR-155wasfurtherverifiedusingreal-timePCR(0.56fold,p<0.05).BioinformaticstargetpredictionidentifiedFADDandcaspase-3asputa

6、tivetargetsofmiR-155.Furthermore,miR-155inhibitedFADDandcaspase-3expressionbydirectlytargetingtheir3-UTRs,whichwasabolishedbymutationofthemiR-155bindingsites.Invitroup-regulationofmiR-155inhumanNPcellsbytransfectionwithlentiviralpre-miR-155resultedinrepressionofFADDandcaspase-3;whereasknockdowno

7、fmiR-155withlentiviralantigomiR-155ledtoover-expressionofFADDandcaspase-3.Also,Fas-mediatedapoptosiswasincreasedwhenantagonizingmiR-155anddecreasedwhenusingpre-miR-155inhumanNPcells.Inaddition,wepresenteddirectevidence

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