Abstract
The aim of this study was to investigate the detailed role and molecular mechanism of long noncoding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in cardiac hypertrophy. Cardiac hypertrophy was established by transverse abdominal aortic constriction (TAC) in vivo or angiotensin II (Ang II) treatment in vitro. Levels of lncRNA TUG1, miR-497 and myocyte enhancer factor 2C (MEF2C) mRNA were assessed by quantitative reverse transcriptase PCR (qRT-PCR). Western blot assay was performed to determine the expression of MEF2C protein. The endogenous interactions among TUG1, miR-497 and MEF2C were confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. Our data indicated that TUG1 was upregulated and miR-497 was downregulated in the TAC rat model and Ang II-induced cardiomyocytes. TUG1 knockdown or miR-497 overexpression alleviated the hypertrophy induced by Ang II in cardiomyocytes. Moreover, TUG1 acted as a sponge of miR-497, and MEF2C was directly targeted and repressed by miR-497. miR-497 overexpression mediated the protective role of TUG1 knockdown in Ang II-induced cardiomyocyte hypertrophy. MEF2C was a functional target of miR-497 in regulating Ang II-induced cardiomyocyte hypertrophy. In addition, TUG1 regulated MEF2C expression through sponging miR-497. Knockdown of TUG1 rescued Ang II-induced hypertrophy in cardiomyocytes at least partly through targeting the miR-497/MEF2C axis, highlighting a novel promising therapeutic target for cardiac hypertrophy treatment.
Highlights
Cardiac hypertrophy is a common physiological compensatory response of the heart against a number of stressors to maintain normal cardiac function
3.1 taurine upregulated gene 1 (TUG1) level was upregulated in the transverse abdominal aortic constriction (TAC) rat model and angiotensin II (Ang II)-induced cardiomyocytes
Ang II treatment remarkably increased the levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) in cardiomyocytes (Figure A1i and j)
Summary
Cardiac hypertrophy is a common physiological compensatory response of the heart against a number of stressors to maintain normal cardiac function. Enlargement of the heart in response to myocardial injury, hypertensive stress or excessive neurohumoral activation is associated with maladaptive remodeling and cardiac dysfunction and is classified as pathological hypertrophy [1]. Long noncoding RNAs (lncRNAs) are more than 200 nucleotide RNA molecules that perform various functions in a series of important biological processes [6]. They have been discovered to have relevance to human diseases, including cardiac hypertrophy [7]. Wang et al reported that cardiac hypertrophy-related factor (CHRF) regulated cardiac hypertrophy by acting as a sponge of microRNA (miRNA)-489 [8]. We identified the functional role and the underlying mechanisms of TUG1 in cardiac hypertrophy
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