title: miR-21-3p regulates cardiac hypertrophic response by targeting histone deacetylase-8.
abstract: OBJECTIVE
  Growing evidences indicate that microRNAs (miRNAs) are involved in cardiac hypertrophy development. Multiple miRNAs have been identified as diagnostic and prognostic biomarkers of cardiac hypertrophy, as well as potential therapeutic tools. The present study aimed to investigate the functions and regulatory mechanisms of miR-21-3p in cardiac hypertrophy.
  
  
  RESULTS
  Decreased expression of miR-21-3p was observed in cardiac hypertrophy induced by transverse aortic constriction (TAC) and angiotensin (Ang) II infusion in mice. To further explore the role of miR-21-3p in cardiac hypertrophy, rAAV-miR-21-3p was administered intravenously in mice. Overexpression of miR-21-3p markedly suppressed TAC-induced cardiac hypertrophy and also blocked Ang II-induced cardiac hypertrophy as determined by cardiac function measurement and biomarker detection. Furthermore, western blot assays showed that histone deacetylase-8 (HDAC8) was silenced by miR-21-3p, and luciferase reporter assays showed that miR-21-3p binds to the 3' UTR of HDAC8. Moreover, re-expression of HDAC8 attenuated miR-21-3p-mediated suppression of cardiac hypertrophy by enhancing phospho-Akt and phospho-Gsk3β expression.
  
  
  CONCLUSIONS
  Our data reveal a role of miR-21-3p in regulating HDAC8 expression and Akt/Gsk3β pathway, and suggest that modulation of miR-21-3p levels may provide a therapeutic approach for cardiac hypertrophy.
authors.affiliation: Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China.
authors.forename: Mengwen
authors.initials: M
authors.lastname: Yan
authors.affiliation: Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China.
authors.forename: Sandip
authors.initials: S
authors.lastname: Chaugai
authors.affiliation: Department of Internal Medicine, Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China dwwang@tjh.tjmu.edu.cn.
authors.forename: Dao Wen
authors.initials: DW
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000818:Animals; D001665:Binding Sites; D006332:Cardiomegaly / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D057809:HEK293 Cells; D006439:Hemodynamics; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D049690:History, Ancient; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D016277:Ventricular Function, Left
chemical_list: D020413:3' Untranslated Regions; C524940:MIRN21 microRNA, human; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D012097:Repressor Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; C409470:HDAC8 protein, human; C000603105:HDAC8 protein, mouse; D006655:Histone Deacetylases
keywords: Cardiac hypertrophy; HDAC; miRNA