title: microRNA-10a Targets T-box 5 to Inhibit the Development of Cardiac Hypertrophy.
abstract: The mechanism of cardiac hypertrophy involving microRNAs (miRNAs) is attracting increasing attention. Our study aimed to investigate the role of miR-10a in cardiac hypertrophy development and the underlying regulatory mechanism.Transverse abdominal aortic constriction (TAAC) surgery was performed to establish a cardiac hypertrophy rat model, and angiotensin II (AngII) was used to induce cardiac hypertrophy in cultured neonatal rat cardiomyocytes. Expression of T-box 5 (TBX5) and miR-10a was altered by cell transfection of siRNA or miRNA mimic/inhibitor. Leucine incorporation assay, histological and cytological examination, quantitative real-time PCR (qRT-PCR), and Western blot were performed to detect the effects of miR-10a and TBX5 on cardiac hypertrophy. Dual-luciferase reporter assay was conducted to verify the regulation of TBX5 by miR-10a.miR-10a was down-regulated, and TBX5 was up-regulated in the rat model and AngII-stimulated cardiomyocytes. miR-10a inhibited TBX5 expression by directly targeting the binding site in Tbx5 3'UTR. Overexpression of miR-10a in AngII-treated cardiomyocytes decreased relative cell area, and significantly reduced the mRNA levels of natriuretic peptide A (Nppa), myosin heavy chain 7 cardiac muscle beta (Myh7), and leucine incorporation (P < 0.01 or P < 0.001). Knockdown of Tbx5 had similar effects on AngII-induced cardiomyocytes.Our findings indicate that miR-10a may inhibit cardiac hypertrophy via targeting Tbx5. Thus, miR-10a provides promising therapeutic strategies for the treatment of cardiac hypertrophy.
authors.affiliation: Fifth Department of Cardiology, Zhengzhou Central Hospital.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Guanqun
authors.initials: G
authors.lastname: Zhai
authors.forename: Yangfei
authors.initials: Y
authors.lastname: Ji
authors.forename: Haiyun
authors.initials: H
authors.lastname: Jing
mesh_terms: D000804:Angiotensin II; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D011897:Random Allocation; D017208:Rats, Wistar; D020825:T-Box Domain Proteins / Q000378:metabolism*
chemical_list: C000603309:MIRN10 microRNA, rat; D035683:MicroRNAs; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; D000804:Angiotensin II