title: MiR-221 promotes cardiac hypertrophy in vitro through the modulation of p27 expression.
abstract: Cardiac hypertrophy has been known as an independent predictor for cardiovascular morbidity and mortality. Molecular mechanisms underlying the development of heart failure remain elusive. Recently, microRNAs (miRs) have been established as important regulators in cardiac hypertrophy. Here, we reported miR-221 was up-regulated in both transverse aortic constricted mice and patients with hypertrophic cardiomyopathy (HCM). Forced expression of miR-221 by transfection of miR-221 mimics increased myocyte cell size and induced the re-expression of fetal genes, which were inhibited by the knockdown of endogenous miR-221 in cardiomyocytes. The TargetScan algorithm-based prediction identified that p27, a cardiac hypertrophic suppressor, is the putative target of miR-221, which was confirmed by luciferase assay and Western blotting. In conclusion, our results demonstrated that miR-221 regulated cardiomyocyte hypertrophy probably through down-regulation of p27, suggesting that miR-221 may be a new intervention target for cardiac hypertrophy.
authors.affiliation: Sino-German Laboratory for Molecular Medicine, State Key Laboratory of Translational Cardiovascular Medicine, Fuwai Hospital & Cardiovascular Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, PR China.
authors.forename: Changxin
authors.initials: C
authors.lastname: Wang
authors.forename: Shuiyun
authors.initials: S
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Wang
authors.forename: Jizheng
authors.initials: J
authors.lastname: Wang
authors.forename: Yilu
authors.initials: Y
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.forename: Yubao
authors.initials: Y
authors.lastname: Zou
authors.forename: Rutai
authors.initials: R
authors.lastname: Hui
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: C546122:MIRN221 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D050760:Cyclin-Dependent Kinase Inhibitor p27