Abstract
BackgroundCardiac hypertrophy associated with various cardiovascular diseases results in heart failure and sudden death. A clear understanding of the mechanisms of hypertrophy will benefit the development of novel therapies. Long non-coding RNAs (lncRNAs) have been shown to play essential roles in many biological process, however, whether lncRNA-ROR plays functional roles in the reprogramming of cardiomyocyte remains unclear.Methodology/Principal FindingsHere we show that lncRNA-ROR plays important roles in the pathogenesis of cardiac hypertrophy. In hypertrophic heart and cardiomyocytes, the expression of lncRNA-ROR is dramatically increased, downregulation of which attenuates the hypertrophic responses. Furthermore, the expression of lncRNA-ROR negatively correlates with miR-133, whose expression is increased when lncRNA-ROR is knocked down. In line with this, overexpression of miR-133 prevents the elevation of lncRNA-ROR and re-expression of ANP and BNP in cardiomyocytes subject to phenylephrine treatment.Conclusions/SignificanceTaken together, our study demonstrates that lncRNA-ROR promotes cardiac hypertrophy via interacting with miR-133, indicating that lncRNA-ROR could be targeted for developing novel antihypertrophic therapeutics.
Highlights
Cardiac hypertrophy, characterized by the increased mass of the heart, is the compensatory remodeling of the heart in response to mechanical stress or neurohormonal stimulation [1]
To explore the role of Long non-coding RNAs (lncRNAs)-ROR in vitro, we examined the expression of lncRNA-ROR in an in vitro model of cardiomyocyte hypertrophy generated by treating cultured neonatal cardiomyocytes with 20 μM phenylephrine (PE), which is widely employed to induce cardiomyocyte hypertrophy [16,17]
Cardiac hypertrophy involves the growth of myocytes as a result of re-expression of fetal genes and enhanced protein synthesis
Summary
Cardiac hypertrophy, characterized by the increased mass of the heart, is the compensatory remodeling of the heart in response to mechanical stress or neurohormonal stimulation [1]. This phenomenon is present in a variety of cardiovascular diseases, including hypertension, valvular disease, and heart failure. Gene expression reprogramming is the base of pathological cardiomyocyte hypertrophy. Accumulating studies have suggested the significant roles of many transcriptional factors, such as the GATA family transcriptional factors, myocyte enhancer factor 2 (MEF2) transcriptional factors, and the homeobox transcriptional factor, in the re-expression of these fetal genes and cardiomyocyte hypertrophy [6]. Editor: Guo-Chang Fan, University of Cincinnati, College of Medicine, UNITED STATES
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