Differential Expression of MicroRNAs in Tumors from Chronically Inflamed or Genetic (APCMin+) Models of Colon Cancer 英文参考文献.docVIP

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Differential Expression of MicroRNAs in Tumors from Chronically Inflamed or Genetic (APCMin+) Models of Colon Cancer 英文参考文献.doc

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DifferentialExpressionofMicroRNAsinTumorsfromChronicallyInflamedorGenetic(APCMin)ModelsofColonCancer英文参考文献

DifferentialExpressionofMicroRNAsinTumorsfrom ChronicallyInflamedorGenetic(APCMin/+)Modelsof ColonCancer BrianM.Necela1,JenniferM.Carr1,YanW.Asmann2,E.AubreyThompson1* 1DepartmentofCancerBiology,MayoClinicComprehensiveCancerCenter,Jacksonville,Florida,UnitedStatesofAmerica, 2DepartmentofBiomedicalStatisticsand Informatics,MayoClinicCollegeofMedicine,Rochester,Minnesota,UnitedStatesofAmerica Abstract Background:Chronicinflammationassociatedwithulcerativecolitispredisposesindividualstoincreasedcoloncancerrisk. TheaimofthesestudieswastoidentifymicroRNAsthatareaberrantlyregulatedduringinflammationandmayparticipate intransformationofcolonicepithelialcellsintheinflammatorysetting. Methodology/PrincipalFindings:WehaveusequantitativePCRarraystocomparemicroRNA(miRNA)expressionintumors mice.Rankorder Min/+ andcontrolcolonicepithelialcellsisolatedfromdistalcolonsofchronicallyinflamedmiceandAPC statisticswasutilizedtoidentifydifferentiallyregulatedmiRNAsintumorsthataroseduetochronicinflammationand/orto germlineAPCmutation.EighthighprioritymiRNAswereidentified:miR-215,miR-137,miR-708,miR-31,andmiR-135bwere differentiallyexpressedinAPCtumorsandmiR-215,miR-133a,miR-467d,miR-218,miR-708,miR-31,andmiR-135bincolitis- associated tumors. Four of these (miR-215, miR-708, miR-31, and miR-135b) were common to both tumors types, and dysregulation of these miRNAs was confirmed in an independent sample set. Target prediction and pathway analysis suggeststhatthesemicroRNAs,intheaggregate,regulatesignalingpathwaysrelatedtoMAPK,PI3K,WNT,andTGF-b,allof whichareknowntobeinvolvedintransformation. Conclusions/Significance:WeconcludethatthesefourmiRNAsaredysregulatedatsomeveryearlystageintransformation ofcolonicepithelialcells.Thisresponseisnotdependentonthemechanismofinitiationoftransformation(inflammation versus germline mutation), suggesting that the miRNAs that we have identified are likely to regulate critical signaling pathwaysthatarecentraltoearlyeventsintransformationofcolonicepith