CD95 Is Part of a Let-7p53miR-34 Regulatory Network 英文参考文献.docVIP

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CD95 Is Part of a Let-7p53miR-34 Regulatory Network 英文参考文献.doc

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CD95 Is Part of a Let-7p53miR-34 Regulatory Network 英文参考文献

CD95IsPartofaLet-7/p53/miR-34RegulatoryNetwork AnnikaHau,PaoloCeppi,MarcusE.Peter* FeinbergSchoolofMedicine,DivisionHematology/Oncology,NorthwesternUniversity,Chicago,Illinois,UnitedStatesofAmerica Abstract ThedeathreceptorCD95(APO-1/Fas)mediatesapoptosisinductionuponligationbyitscognateligandCD95L.Twotypes ofCD95signalingpathwayshavebeenidentified,whicharecharacterizedbytheabsence(TypeI)orpresence(TypeII)of mitochondrialinvolvement.Micro(mi)RNAsaresmallnoncodingRNAsthatnegativelyregulategeneexpression.Theyare importantregulatorsofdifferentiationprocessesandarefoundfrequentlyderegulatedinmanyhumancancers.Werecently showedthatTypeIcellsexpresslessofthedifferentiationmarkermiRNAlet-7and,hence,likelyrepresentmoreadvanced tumorcellsthanthelet-7highexpressingTypeIIcells.WehavenowidentifiedmiR-34aasaselectivemarkerforcellsthat are sensitive to CD95-mediated apoptosis. Both CD95 and miR-34a are p53 target genes, and consequently, both the sensitivityofcancercellstoCD95-mediatedapoptosisandtheabilitytorespondtop53mediatedDNAgenotoxicstressare linked.Interestingly,whilemiR-34awasfoundtopositivelycorrelatewiththeabilityofcellstorespondtogenotoxicstress, let-7wasnegativelycorrelated.TheexpressionlevelofCD95inverselycorrelatedwiththeexpressionoflet-7suggesting regulationoflet-7expressionbyCD95.Totestalinkbetweenp53andmiR-34a,wealteredtheexpressionofCD95.This affectedtheabilityofcellstoactivatep53andtoregulatemiR-34a.Ourdatapointtoanovelregulatorynetworkcomprising p53, CD95, let-7, and miR-34a that affects cancer cell survival, differentiation, and sensitivity to apoptotic signals. The possiblerelevanceofthisregulatorynetworkforcancerstemcellsisdiscussed. Citation:HauA,CeppiP,PeterME(2012)CD95IsPartofaLet-7/p53/miR-34RegulatoryNetwork.PLoSONE7(11):e49636.doi:10.1371/journal.pone.0049636 Editor:AndreiL.Gartel,UniversityofIllinoisatChicago,UnitedStatesofAmerica ReceivedMay30,2012;AcceptedOctober16,2012;PublishedNovember14,2012 Copyright:?2012Hauetal.Thisisanopen-accessarticledis