NucleicAcidsResearch,20191doi:10.1093/nar/gky1012IGF2BP1promotesSRF-dependenttranscriptionincancerinam6A-andmiRNA-dependentmannerSimonM¨uller1,MarkusGlaß1,AnuragK.Singh2,JacobHaase1,NadineBley1,TommyFuchs1,MarcellLederer1,AndreasDahl3,HuilinHuang4,5,JianjunChen4,5,GuidoPosern2andStefanH¨uttelmaier1,*1InstituteofMolecularMedicine,SectionforMolecularCellBiology,FacultyofMedicine,MartinLutherUniversityHalle-Wittenberg,CharlesTanfordproteincenter,Kurt-Mothes-Str.3a,06120Halle,Germany,2InstituteforPhysiologicalChemistry,MedicalFaculty,MartinLutherUniversityHalle-Wittenberg,06114Halle(Saale),Germany,3DeepSequencingGroup,CenterforMolecularandCellularBioengineering,TechnischeUniversit¨atDresden,Tatzberg47/49,01307Dresden,4DepartmentofSystemsBiology,CityofHope,Monrovia,CA91016,USAand5DepartmentofCancerBiology,UniversityofCincinnatiCollegeofMedicine,Cincinnati,OH45219,USAReceivedJune29,2018;RevisedOctober09,2018;EditorialDecisionOctober10,2018;AcceptedOctober17,2018ABSTRACTTheoncofetalmRNA-bindingproteinIGF2BP1andthetranscriptionalregulatorSRFmodulategeneexpressionincancer.Incancercells,wedemon-stratethatIGF2BP1promotestheexpressionofSRFinaconservedandN6-methyladenosine(m6A)-dependentmannerbyimpairingthemiRNA-directeddecayoftheSRFmRNA.Thisresultsinen-hancedSRF-dependenttranscriptionalactivityandpromotestumorcellgrowthandinvasion.Atthepost-transcriptionallevel,IGF2BP1sustainstheex-pressionofvariousSRF-targetgenes.ThemajorityoftheseSRF/IGF2BP1-enhancedgenes,includingPDLIM7andFOXK1,showconservedupregulationwithSRFandIGF2BP1synthesisincancer.PDLIM7andFOXK1promotetumorcellgrowthandwerereportedtoenhancecellinvasion.Consistently,35SRF/IGF2BP1-dependentgenesshowingconservedassociationwithSRFandIGF2BP1expressionin-dicateapooroverallsurvivalprobabilityinovar-ian,liverandlungcancer.Inconclusion,thesefind-ingsidentifytheSRF/IGF2BP1-,miRNome-andm6A-dependentcontrolofgeneexpressionasacon-servedoncogenicdrivernetworkincancer.INTRODUCTIONThemammalianIGF2mRNAbindingproteins(IGF2BPs;ali...
