Nuclear miR-665 aggravates heart failure via suppressing phosphatase and tensin homolog transcription  

作　　者：Jiahui Fan Xudong Zhang Xiang Nie Huaping Li Shuai Yuan Beibei Dai Jiabing Zhan Zheng Wen Jiangang Jiang Chen Chen Daowen Wang 

机构地区：[1]Division of Cardiology,Department of Internal Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [2]Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders,Wuhan 430030,China

出　　处：《Science China(Life Sciences)》2020年第5期724-736,共13页中国科学（生命科学英文版）

基　　金：supported by grant from the National Natural Science Foundation of China(81822002,81630010,81790624,91839302,31771264 and 31800973)。

摘　　要：Although numerous miRNAs have been discovered,their functions in the different subcellular organelles have remained obscure.In this study,we found that miR-665 was enriched in the nucleus of cardiomyocytes,and then investigated the underlying role of nuclear miR-665 in heart failure.RNA fluorescence in situ hybridization assays in human heart tissue sections and primary cardiomyocytes showed that miR-665 was localized in the nucleus of cardiomyocytes.Increased expression of nuclear miR-665 was observed not only in the cardiomyocytes isolated from the heart of mice treated in vivo by transverse aortic constriction(TAC),but also in phenylephrine(PE)-treated cultured cardiomyocytes in vitro.To further explore the role of miR-665 in heart failure,a type 9 recombinant adeno-associated virus(rAAV)system was employed to manipulate the expression of miR-665 in mice.Overexpression of miR-665 aggravated TAC-induced cardiac dysfunction,while down-expression of miR-665 showed opposite effects.Bioinformatic prediction and biological validation confirmed that the PTEN(phosphatase and tensin homolog)gene was one of the targets of miR-665 in the nucleus.Furthermore,restoring PTEN expression significantly eliminated the destructive effects of miR-665 over-expression in TAC-induced cardiac dysfunction.Our data showed that nuclear miR-665 aggravates heart failure via inhibiting PTEN expression,which provided a therapeutic approach for heart failure.

关 键 词：nucleus miR-665 heart failure phosphatase and tensin homolog 

分 类 号：R541.6[医药卫生—心血管疾病]