Circular RNA circ_0010729 Knockdown Attenuates Oxygen-Glucose Deprivation-Induced Human Cardiac Myocytes Injury by miR-338-3p/CALM2 Axis

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY(2021)

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Abstract
Circular RNAs have pivotal roles in cardiovascular disease. The injury of cardiac myocytes is associated with occurrence of cardiovascular disease. Circular RNA hsa_circ_0010729 (circ_0010729) is associated with cardiac myocytes injury. However, the mechanism of circ_0010729 in cardiac myocytes injury remains largely unclear. In our study, cardiac myocytes were treated by oxygen-glucose deprivation (OGD). The abundances of circ_0010729, microRNA-338-3p (miR-338-3p), and calmodulin 2 (CALM2) were detected by quantitative reverse transcription polymerase chain reaction or Western blot. OGD-induced damage in AC16 cells was assessed by cell viability, apoptosis, and autophagy using Cell Counting Kit-8, flow cytometry, and Western blot analyses. The target relationship of miR-338-3p and circ_0010729 or CALM2 was explored by starBase and dual-luciferase reporter analysis. Our results showed that the circ_0010729 level was enhanced in OGD-treated AC16 cells and murine primary cardiac myocytes. circ_0010729 silence weakened OGD-induced viability inhibition and promotion of apoptosis and autophagy in AC16 cells and murine primary cardiac myocytes. miR-338-3p was sponged by circ_0010729 and miR-338-3p knockdown alleviated the effect of circ_0010729 silence on OGD-induced damage. miR-338-3p directly targeted CALM2 to inhibit OGD-induced damage in AC16 cells. circ_0010729 could regulate CALM2 expression by sponging miR-338-3p. Collectively, circ_0010729 interference mitigated OGD-induced damage in cardiac myocytes through increasing cell viability and inhibiting apoptosis and autophagy by regulating miR-338-3p/CALM2 axis. This study indicated circ_0010729 might act as a target for treatment of cardiovascular disease.
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Key words
cardiovascular disease, circ_0010729, miR-338-3p, CALM2, oxygen-glucose deprivation, human cardiac myocytes
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