microRNA-10a Targets T-box 5 to Inhibit the Development of Cardiac Hypertrophy

Abstract

SummaryThe 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. (Int Heart J 2017; 58: 100-106)

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“…More than 1,500 different miRNAs have been identified in human genome, and many of them were proved to be involved in cardiovascular development, function, and development of disease. [5][6][7][8] In the cardiovascular-related miRNAs, miR-208a earned more attention as a heart-enriched miRNA. It was considered as a potential biomarker or therapeutic target for the treatment of heart disease.…”

Evolution of Vertebrate Ryanodine Receptors Family in Relation to Functional Divergence and Conservation

“…[1][2][3] Ryanodine receptor (RyR) is one family of intracellular Ca 2+ release channels which regulates the release of Ca 2+ from the endoplasmic reticulum or sarcoplasmic reticulum into the cytosol. 4) RyR is the largest known ion channel, in form of homotetramers (approximately 2,200 kDa), each subunit of which is comprised of a large N-terminal cytoplasmic domain, accounting for 4/5 of the protein, that modulates the gating of the channel, and 1/5 proportion being luminal and transmembrane spanning (TM) domains.…”

MicroRNA as a Therapeutic Target in Cardiac Remodeling

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