miR-328FunctionsasanRNADecoytoModulatehnRNPE2RegulationofmRNATranslationinLeukemicBlastsAnnaM.Eiring,1JasonG.Harb,1PaoloNeviani,1ChristopherGarton,1JoshuaJ.Oaks,1RiccardoSpizzo,6ShujunLiu,2SebastianSchwind,2,3RamasamySanthanam,1ChristopherJ.Hickey,2,3HeikoBecker,2,3JasonC.Chandler,2RaulAndino,5JorgeCortes,6PeterHokland,7ClaudiaS.Huettner,8RaviBhatia,9DenisC.Roy,10StephenA.Liebhaber,11MichaelA.Caligiuri,1,2,3GuidoMarcucci,1,2,3RamiroGarzon,1,2,3CarloM.Croce,1,3GeorgeA.Calin,6andDaniloPerrotti1,3,4,*1HumanCancerGeneticsProgram,DepartmentofMolecularVirology,Immunology,andMedicalGenetics2DepartmentofInternalMedicine3ComprehensiveCancerCenter4CenterforRNABiologyTheOhioStateUniversity,Columbus,OH43210,USA5DepartmentofMicrobiology&Immunology,UniversityofCalifornia,SanFrancisco,CA94143,USA6DepartmentofLeukemiaandDepartmentofExperimentalTherapeutics,CenterforRNAInterferenceandNon-CodingRNAs,M.D.AndersonCancerCenter,Houston,TX77030,USA7DepartmentofHematology,AarhusUniversity,8000AarhusC,Denmark8DanaFarberCancerInstitute,HarvardMedicalSchool,Boston,MA02115,USA9DepartmentofHematopoieticStemCellandLeukemiaResearch,CityofHopeNationalMedicalCenter,Duarte,CA91010,USA10DepartmentofHematology-Oncology,Maisonneuve-RosemontHospitalandUniversityofMontreal,Montreal,QuebecH3T1J4,Canada11DepartmentofGeneticsandMedicine,UniversityofPennsylvaniaSchoolofMedicine,Philadelphia,PA19104,USA*Correspondence:danilo.perrotti@osumc.eduDOI10.1016/j.cell.2010.01.007SUMMARYMicroRNAsandheterogeneousribonucleoproteins(hnRNPs)areposttranscriptionalgeneregulatorsthatbindmRNAinasequence-specificmanner.Here,wereportthatlossofmiR-328occursinblastcrisischronicmyelogenousleukemia(CML-BC)inaBCR/ABLdose-andkinase-dependentmannerthroughtheMAPK-hnRNPE2pathway.RestorationofmiR-328expressionrescuesdifferentiationandimpairssurvivalofleukemicblastsbysimultaneouslyinteractingwiththetranslationalregulatorpoly(rC)-bindingproteinhnRNPE2andwiththemRNAencodingthesurvivalfactorPIM1,respectively.TheinteractionwithhnRNPE2isind...
