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PublishedOnlineFirstAugust15,2013.CancerRes LeiZhang,KarenPickard,VeronikaJenei,etal. effectsthatenhanceinvasionandchemotherapeuticresistancemiR-153supportscolorectalcancerprogressionviapleiotropic Updatedversion 10.1158/0008-5472.CAN-12-3308doi:Accessthemostrecentversionofthisarticleat: MaterialSupplementary : ManuscriptAuthoredited.Authormanuscriptshavebeenpeerreviewedandacceptedforpublicationbuthavenotyetbeen E-mailalertsrelatedtothisarticleorjournal.Signuptoreceivefreeemail-alerts SubscriptionsReprintsand .pubs@aacr.orgDepartmentatToorderreprintsofthisarticleortosubscribetothejournal,contacttheAACRPublications Permissions .permissions@aacr.orgDepartmentatTorequestpermissiontore-useallorpartofthisarticle,contacttheAACRPublicationsResearch.onAugust28,2013.©2013AmericanAssociationforCancercancerres.aacrjournals.orgDownloadedfromAuthormanuscriptshavebeenpeerreviewedandacceptedforpublicationbuthavenotyetbeenedited.AuthorManuscriptPublishedOnlineFirstonAugust15,2013;DOI:10.1158/0008-5472.CAN-12-33081TitlemiR-153supportscolorectalcancerprogressionviapleiotropiceffectsthatenhanceinvasionandchemotherapeuticresistanceShorttitlemiR-153supportscolorectalcancerprogressionPrecisMicroRNAsthatfacilitateprogressionandmediatedrugresistanceinadvancedcancershaveincreasedappealastreatmenttargets,giventhemorefrequentlackofeffectivetherapiesatlatestagesofdisease.AuthorsLeiZhang1*,KarenPickard1*,VeronikaJenei1*,MarcD.Bullock1,AmandaBruce1,RichardMitter2,GavinKelly2,ChristosParaskeva3,JohnStrefford1,JohnPrimrose1,GarethJ.Thomas1†,GrahamPackham1†,AlexH.Mirnezami1,4.*,†Theseauthorscontributedequallytothisstudy.Institutions1.UniversityofSouthamptonCancerSciencesDivision,SomersCancerResearchBuilding,SouthamptonUniversityHospitalNHSTrust,Tremonaroad,Southampton,UK.2.BioinformaticsUnit,LondonResearchInstitute,CancerResearchUK,London.3.SchoolofCellularandMolecularMedicine,UniversityofBristol,MedicalSciencesBuilding,Bristol,UK.Research.onAugust28,2013.©2013AmericanAssociationforCancercancerres.aacrjournals.orgDownloadedfromAuthormanuscriptshavebeenpeerreviewedandacceptedforpublicationbuthavenotyetbeenedited.AuthorManuscriptPublishedOnlineFirstonAugust15,2013;DOI:10.1158/0008-5472.CAN-12-330824.DepartmentofColorectalSurgery,SouthamptonUniversityHospitalNHSTrust,Tremonaroad,Southampton,UK.CorrespondanceMr.A.H.Mirnezami,CancerResearchUKandRoyalCollegeofSurgeonsofEnglandClinicianScientist,SomersCancerResearchBuilding,UniversityofSouthamptonCancerSciencesDivision,SouthamptonUniversityHospitalNHSTrust,Tremonaroad,SO166YD.Southampton,UK.Email:ahm@soton.ac.ukTelephone:07775507050AuthorcontributionsLZ–acquisitionofdata,analysis,interpretationKP-acquisitionofdata,analysis,interpretationVJ-acquisitionofdata,analysis,interpretationMB-acquisitionofdata,analysis,interpretationAB-acquisitionofdata,analysis,RM-acquisitionofdata,analysis,interpretation,statisticalanalysisGK-acquisitionofdata,analysis,interpretation,statisticalanalysisCP–provisionofkeymaterialandinputintostudydesignJC-acquisitionofdata,analysis,interpretation,technicalsupportJNP–studyconcept,analysis,criticalappraisalResearch.onAugust28,2013.©2013AmericanAssociationforCancercancerres.aacrjournals.orgDownloadedfromAuthormanuscriptshavebeenpeerreviewedandacceptedforpublicationbuthavenotyetbeenedited.AuthorManuscriptPublishedOnlineFirstonAugust15,2013;DOI:10.1158/0008-5472.CAN-12-33083GT–Analysis,criticalappraisal,technicalandmaterialsupportGP–Studyconceptanddesign,analysis,criticalappraisal,technicalsupportAHM–Studyconceptanddesign,acquisitionofdata,analysis,interpretation,draftingofmanuscript,obtainedfunding,studysupervisionManuscriptcategoryOriginalarticleWordcount4443KeywordsColorectalcancer,miR-153,MMP9,FOXO3a,chemoresistanceAbbreviationsCRC,colorectalcancer;FOXO3a,ForkheadboxO3transcriptionfactor;MiRNA,microRNA;MMP9,matrixmetalloprotease9.AcknowledgementsKPandAHMaresupportedbygrantfundingfromWessexMedicalResearchandCancerResearchUK/RCS(England)(C28503/A10013).ConflictofinterestTheauthorsdisclosenopotentialconflictsofinterest.FundingCancerResearchUKandtheRoyalCollegeofSurgeonsofEngland;WessexMedicalResearchResearch.onAugust28,2013.©2013AmericanAssociationforCancercancerres.aacrjournals.orgDownloadedfromAuthormanuscriptshavebeenpeerreviewedandacceptedforpublicationbuthavenotyetbeenedited.AuthorManuscriptPublishedOnlineFirstonAugust15,2013;DOI:10.1158/0008-5472.CAN-12-33084AbstractWhilemicroRNAs(miRNAs)havebeenbroadlystudiedincancer,comparativelylessisunderstoodabouttheirroleinprogression.HerewereportthatmiR-153hasadualroleduringprogressionofcolorectalcancer(CRC)byenhancingcellularinvasivenessandplatinum-basedchemotherapyresistance.MiRNAprofilingrevealedthatmiR-153washighlyexpressedinacellularmodelofadvancedstageCRC.ItsupregulationwasalsonotedinprimaryhumanCRCcomparedtonormalcolonicepithelium,andinmoreadvancedCRCstagescomparedtoearlystagedisease.InCRCpat