Department of Cardiovascular III, Cangzhou Central Hospital, Cangzhou, Hebei, China.
J Cardiovasc Pharmacol. 2021 May 1;77(5):594-602. doi: 10.1097/FJC.0000000000000988.
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.
环状 RNA 在心血管疾病中具有关键作用。心肌细胞损伤与心血管疾病的发生有关。环状 RNA hsa_circ_0010729(circ_0010729)与心肌细胞损伤有关。然而,circ_0010729 在心肌细胞损伤中的机制在很大程度上仍不清楚。在我们的研究中,用氧葡萄糖剥夺(OGD)处理心肌细胞。通过定量逆转录聚合酶链反应或 Western blot 检测 circ_0010729、microRNA-338-3p(miR-338-3p)和钙调蛋白 2(CALM2)的丰度。用细胞计数试剂盒-8、流式细胞术和 Western blot 分析评估 OGD 诱导的 AC16 细胞损伤。通过 starBase 和双荧光素酶报告分析探讨 miR-338-3p 与 circ_0010729 或 CALM2 的靶关系。结果显示,OGD 处理的 AC16 细胞和鼠原代心肌细胞中 circ_0010729 水平升高。circ_0010729 沉默减弱了 OGD 诱导的 AC16 细胞和鼠原代心肌细胞活力抑制和凋亡和自噬的促进。circ_0010729 可吸附 miR-338-3p,miR-338-3p 敲低减轻了 circ_0010729 沉默对 OGD 诱导损伤的影响。miR-338-3p 直接靶向 CALM2,抑制 AC16 细胞 OGD 诱导的损伤。circ_0010729 可通过吸附 miR-338-3p 调节 CALM2 表达。综上所述,circ_0010729 通过调节 miR-338-3p/CALM2 轴,增加细胞活力,抑制凋亡和自噬,减轻 OGD 诱导的心肌细胞损伤。该研究表明 circ_0010729 可能作为心血管疾病治疗的靶点。