Receptor for Activated Protein Kinase C Requirement for Efficient MicroRNA Function and Reduced Expression in Hepatocellular Carcinoma 英文参考文献.docVIP

ReceptorforActivatedProteinKinaseC:Requirementfor EfficientMicroRNAFunctionandReducedExpressionin HepatocellularCarcinoma MotoyukiOtsuka1*,AkemiTakata1,TakeshiYoshikawa1,KentaroKojima1,TakahiroKishikawa1, ChikakoShibata1,MutsuhiroTakekawa2,HaruhikoYoshida1,MasaoOmata1¤,KazuhikoKoike1 1DepartmentofGastroenterology,GraduateSchoolofMedicine,TheUniversityofTokyo,Tokyo,Japan,2DepartmentofCellSignalingandMolecularMedicine,Research InstituteofEnvironmentalMedicine,NagoyaUniversity,Nagoya,Japan Abstract MicroRNAs (miRNAs) are important regulators of gene expression that control physiological and pathological processes. A global reduction in miRNA abundance and function is a general trait of human cancers, playing a causal role in the transformed phenotype. Here, we sought to newly identify genes involved in the regulation of miRNA function by performing a genetic screen using reporter constructs that measure miRNA function and retrovirus-based random gene disruption. Of the six genes identified, RACK1, which encodes ‘‘receptor for activated protein kinase C’’ (RACK1), was confirmedtobenecessaryforfullmiRNAfunction.RACK1bindstoKH-typesplicingregulatoryprotein(KSRP),amemberof theDicercomplex,andisrequiredfortherecruitmentofmaturemiRNAstotheRNA-inducedsilencingcomplex(RISC).In addition,RACK1expressionwasfrequentlyfoundtobereducedinhepatocellularcarcinoma.Thesefindingssuggestthe involvementofRACK1inmiRNAfunctionandindicatethatreducedmiRNAfunction,duetodecreasedexpressionofRACK1, mayhavepathologicallyrelevantrolesinlivercancers. Citation: Otsuka M, Takata A, Yoshikawa T, Kojima K, Kishikawa T, et al. (2011) Receptor for Activated Protein Kinase C: Requirement for Efficient MicroRNA FunctionandReducedExpressioninHepatocellularCarcinoma.PLoSONE6(9):e24359.doi:10.1371/journal.pone.0024359 Editor:Chun-MingWong,UniversityofHongKong,HongKong ReceivedMay6,2011;AcceptedAugust7,2011;PublishedSeptember15,2011 Copyright: ? 2011 Otsuka et al. This is an open-access article distributed und