RNAi在肿瘤多药耐药中的应用

457RNAi,,3(,410078):RNA;(MDR);siRNA:R318,R394:A:1672-2981(2006)06-0457-04,,,,,RNAi,,RNAi1RNARNA(RNAinterference,RNAi)1990,(petunias),,,(cosuppression)[1]Guo[2]RNA(C1elegans)par1,RNApar1,RNA19982,AndrewFireCraigMello,GuoRNARNARNA,RNA(),RNA(RNAinterference,RNAi)RNARNA2RNA,RNAi[3],RNA(dsRNA)2123RNA(smallinterferingRNA,siRNA);,siRNAmRNARNARNase,Dicer,[4]dsRNARNAi,DicerATPRNA,RNA2123bpRNA(siRNA),siRNA,RNA(RNAinducedsilencingcomplex,RISC)[4]RISCsiR2NA,DicerRNA,mRNA,RISCArgonaute,[5]RISCsiRNA,mRNA,,dsRNAmR2NA,RNAi,RNAi,RNAi,RNAiRNAi,RNARNA(RNAdependentRNApolymerase,RdRP),siRNAdsRNA,DicersiRNA[627],[6],siRNA(30bp)(),RNAi,,30bpsiRNA2123bpsiRNA,mRNA,RNAi[829],siRNA,,mRNAsiRNA,siRNAmRNA90%2132siRNA[10],siRNA,,(positionaleffects)[11]3RNAi311siRNA:,,,Tel:[phone]:,,,,Tel(Fax):[phone]Email:[e-mail]2006,Vol14No16©1994-2008ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[12]RNA(smallhair2pinRNA,shRNA)MCF27CDHl,shRNACDH1,siRNA32312RNAi,90%[13],dsRNA313RNAi,50%80%,1219%27%314Irie[14],RNAi,RNAi,dsR2NA23d,RNAi,12d,mRNAdsRNARNA,siRNA315dsRNADicer200500bpdsRNA,,Dicer,RNAidsR2NA316RNAi,RNAi,RNAiRde2lRde22[15]317RNAi,Van,sid21111318ATPATP,RNAi,RNAi1ATP,DicerRISCATP319RNAi,dsR2NA,RNAiRNAi4RNAiMDRMDR,,,,P(P2glycoprotein,P2gp),(Multi2drugresistanceprotein,MRP),(Breastcancerresistanceprotein,BCRP)WuHaoMDR17999siRNA,,2448hRT2PCRMDR1mRNA,24hP2gpMCF27/Ad2rRsiRNA,(P0101),,(P0105),MCF27/AdrRMCF27/BC219A2780Dx8232494;MCF27/AdrR12,95,siRNA,siR2NA(200nmolL-1),P2gp65%,P2gp(1417h)siR2NAP2gpMCF27/AdrRA2780Dx8DNAsiRNA,P2gp[16]Chris2tiemesiRNAEPP852181RDBEPG852257RDB1dEPG852257RDB,MDR1mRNA,35dMDR1mRNA,7dEPP852181RDB,3dMDR1mRNA,,10dP2gpsiRNA35dsiRNA,MDR1mRNA[17]siRNAK562/A02,K562/A02siRNA,MDR1mRNAP2gp,[18219]YagueEsiRNAK562,[20]5RNAi511siRNAsiRNA2:siRNA;,mRNA(AUG),AA21bpsiRNAmRNARISCmRNA,,mRNA,,blast,,[21222]mRNAsiRNA,34siRNA,siRNA,siRNACentralSouthPharmacy.December2006,Vol14No1620061246©1994-2008ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[23]512siRNAsiRNA2:siRNA,;siRNA,siRNAsiRNARNA(RNase)dsRNA[24],RNasedsRNA[23],,,siRNA,,,siR2NA,siRNAsiRNADNA,RNA(RNApol)(U6U6H1),siRNA,SuiGBS/U6/laminA/CBS/U6/cdk22,siRNA,laminA/Ccdk22siRNA,,siRNA[22]siRNA,BrummelkampTRpSUPERsiRNADNA(19bp)RNApolH1,5(T)RNApo,CDH1siRNA,pSUPER,,3pSUPER5bp7bp9bpsiRNA,,siRNA,9bpsiRNA,7bp,5bpsiRNA[25]25d[26227],siRNA(SECs),PCR5RNApol,3RNApol(34U),siRNADNA,SECs,6RNAi,siRNA,:,P2gp,,P2gp,2,,siRNAP2gp,,siRNA[1]vanderKrolAR,MurLA,deLangeP,etal1InhibitionofflowerpigmentationbyantisenseCHSgenes:promoterandminimalsequencerequirementsfortheantisenseeffect[J].PlantMolBiol,1990,14(4):45724661[2]GuoS,KemphuesKJ1Par21,agenerequiredforestablishingpolarityinC1elegansembryos,encodesaputativeSer/Thrki2nasethatisasymmetricallydistributed[J].Cell,1995,81(4):61126201[3]DenliAM,HannonGJ1RNAi:anever2growingpuzzle[J].TrendsBiochemSci,2003,28(4):19622011[4]HannonGJ1RNAinterference[J].Nature,2002,418(6894):24422511[5]CarmellMA,XuanZ,ZhangMQ,etal1TheArgonautefami2ly:tentaclesthatreachintoRNAi,developmentalcontrol,stemcellmaintenance,andtumorigenesis[J].GenesDev,2002,16(21):2733227421[6]SijenT,FleenorJ,SimmerF,etal1OntheroleofRNAampli2ficationindsRNAtriggeredgenesilencing[J].Cell,2001,107(4):46524761[7]LipardiC,WeiQ,PatersonBM1RNAiasrandomdegradativePCR:siRNAprimersconvertmRNAintodsRNAsthatarede2gradedtogeneratenewsiRNAs[J].Cell,2001,107(3):29723071[8]ElbashirSM,HarborthJ,LendeckelW,etal1Duplexesofnu2cleotideRNAsmediateRNAinterferenceinculturedmammaliancells[J].Nature,2001,411(6836):49424981[9]CaplenNJ,ParrishS,ImaniF,etal1SpecificinhibitionofgeneexpressionbysmalldoublestrandedRNAsininvertebrateandvertebratesystems[J].ProcNatlAcadSciUSA,2001,98(17):9742297471[10]VickersTA,KooS,BennettCF,etal1EfficientreductionoftargetRNAsbysmallinterferingRNAandRNaseH2depend2entantisenseagents1Acomparativeanalysis[J].JBiolChem,2003,278(9):7108271181[11]HolenT,AmarzguiouiM,WiigerMT,etal1PositionaleffectsofshortinterferingRNAstargetingthehumancoagulationtriggerTissueFactor[J].NucleicAcidsRes,2002,30(8):1757217661[12]BrummelkampTR,BernardsR,AgamiR1AsystemforstableexpressionofshortinterferingRNAsinmammaliancells[J].Science,2002,296(5567):55025531[13],1RNA[J].20061246CentralSouthPharmacy.December2006,Vol14No16©1994-2008ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(4):41124171[14]IrieN,SakaiN,UeyamaT,etal1SubtypeandspeciesspecificknockdownofPKCusingshortinterferingRNA[J].BiochemBiophysResCommun,2002,298(5):73827431[15]BrantlS1AntisenseRNAregulationandRNAinterference[J].BiochimBiophysActa,2002,1575(123):152251[16]WuH,HaitWN,YangJMetal1SmallInterferingRNA2in2ducedSuppressionofMDR1(P2Glycoprotein)RestoresSensi2tivitytoMultidrug2resistantCancerCells[J].CancerRes,2003,63(4):1515215191[17]ChristianeN,AxelP,AlexandraS,etal1Modulationoftheclassicalmultidrugresistance(MDR)phenotypebyRNAinter2ference(RNAi)[J].FEBSLetters,2003,545(223):14421