Circular RNA POSTN Promotes Myocardial Infarction-Induced Myocardial Injury and Cardiac Remodeling by Regulating miR-96-5p/BNIP3 Axis
Open Access
- 18 February 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Cell and Developmental Biology
Abstract
Myocardial infarction (MI) is the most prevalent cardiac disease with high mortality, leading to severe heart injury. Circular RNAs (circRNAs) are a new type of regulatory RNAs and participate in multiple pathological cardiac progressions. However, the role of circRNAs Postn (circPostn) in MI modulation remains unclear. Here, we aimed to explore the effect of circPostn on MI-induced myocardial injury and cardiac remodeling. We identified that the expression of circPostn was elevated in the plasma of MI patients, MI mouse model, and hypoxia and reoxygenation (H/R)-treated human cardiomyocytes. The depletion of circPostn significantly attenuated MI-related myocardium injury and reduced the infarct size in MI mouse model. The circPostn knockdown obviously enhanced left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) and inhibited left ventricular anterior wall thickness at diastole (LVAWd) and left ventricular posterior wall thickness at diastole (LVPWd). The depletion of circPostn was able to decrease MI-induced expression of collagen 1α1 and collagen 3α1 in the ventricular tissues of mice. The protein expression of collagen and α-smooth muscle actin (SMA) was up-regulated in MI mice and was inhibited by circPostn knockdown. Meanwhile, the expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was repressed by circPostn depletion in the ventricular tissues of MI mice. Besides, the circPostn depletion attenuated cardiomyocyte apoptosis in mice. Mechanically, circPostn served as a miR-96-5p sponge and miR-96-5p-targeted BNIP3 in human cardiomyocytes, in which circPostn up-regulated BNIP3 expression by targeting miR-96-5p. circPostn promoted H/R-induced cardiomyocyte injury by modulating miR-96-5p/BNIP3 axis. Thus, we conclude that circPostn contributes to MI-induced myocardial injury and cardiac remodeling by regulating miR-96-5p/BNIP3 axis. Our finding provides new insight into the mechanism by which circPostn regulates MI-related cardiac dysfunction. circPostn, miR-96-5p, and BNIP3 are potential targets for the treatment of MI-caused heart injury.Keywords
This publication has 48 references indexed in Scilit:
- Negative Regulation of miR-375 by Interleukin-10 Enhances Bone Marrow-Derived Progenitor Cell-Mediated Myocardial Repair and Function After Myocardial InfarctionThe International Journal of Cell Cloning, 2015
- Inflammation as a therapeutic target in myocardial infarction: learning from past failures to meet future challengesTranslational Research, 2015
- Embryonic Stem Cell–Derived Exosomes Promote Endogenous Repair Mechanisms and Enhance Cardiac Function Following Myocardial InfarctionCirculation Research, 2015
- Regulation of circRNA biogenesisRNA Biology, 2015
- The role of Bcl-2 family member BNIP3 in cell death and disease: NIPping at the heels of cell deathCell Death & Differentiation, 2009
- BNIP3 subfamily BH3-only proteins: mitochondrial stress sensors in normal and pathological functionsOncogene, 2008
- Multilevel Regulation of Gene Expression by MicroRNAsScience, 2008
- Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in miceJCI Insight, 2007
- l‐2‐Hydroxyglutaric aciduria, a defect of metabolite repairJournal of Inherited Metabolic Disease, 2007
- BNip3 and signal-specific programmed death in the heartJournal of Molecular and Cellular Cardiology, 2005