CircHIPK3 regulates the autophagy and apoptosis of hypoxia/reoxygenation-stimulated cardiomyocytes via the miR-20b-5p/ATG7 axis

Abstract

Autophagy and apoptosis are involved in myocardial ischemia/reperfusion (I/R) injury. Research indicates that circular RNA HIPK3 (circHIPK3) is crucial to cell autophagy and apoptosis in various cancer types. However, the role of circHIPK3 in the regulation of cardiomyocyte autophagy and apoptosis during I/R remains unknown. Our study aimed to examine the regulatory effect of circHIPK3 during myocardial I/R and investigate its mechanism in cardiomyocyte autophagy and apoptosis. Methods and results. The expression of circHIPK3 was upregulated during myocardial I/R injury and hypoxia/reoxygenation (H/R) injury of cardiomyocytes. To study the potential role of circHIPK3 in myocardial H/R injury, we performed gain-of-function and loss-of-function analyses of circHIPK3 in cardiomyocytes. Overexpression of circHIPK3 significantly promoted H/R-induced cardiomyocyte autophagy and cell injury (increased intracellular reactive oxygen species (ROS) and apoptosis) compared to those in the control group, while silencing of circHIPK3 showed the opposite effect. Further research found that circHIPK3 acted as an endogenous miR-20b-5p sponge to sequester and inhibit miR-20b-5p activity, resulting in increased ATG7 expression. In addition, miR-20b-5p inhibitors reversed the decrease in ATG7 induced by silencing circHIPK3. Conclusions. CircHIPK3 can accelerate cardiomyocyte autophagy and apoptosis during myocardial I/R injury through the miR-20b-5p/ATG7 axis. These data suggest that circHIPK3 may serve as a potential therapeutic target for I/R.

Long non-coding RNA growth arrest specific transcript 5 acting as a sponge of MicroRNA-188-5p to regulate SMAD family member 2 expression promotes myocardial ischemia-reperfusion injury

“…The H/R model was established by referring to the previous method [ 17 ]. HL-1 cells from the Chinese Academy of Sciences (Shanghai) were cultured in Dulbecco’s Modified Eagle Medium (DMEM) (Gibco-BRL, Grand Island, NY) at 37°C with 5% CO 2 , and seeded in the logarithmic growth phase into 24-well plates.…”

Purple sweet potato delphinidin-3-rutin represses glioma proliferation by inducing miR-20b-5p/Atg7-dependent cytostatic autophagy

“…For example, Qiu and colleagues proved that, in myocardial cells, circular RNA HIPK3 (circHIPK3) regulated the autophagy and apoptosis of hypoxia/reoxygenation-stimulated cardiomyocytes through the miR-20b-5p/Atg7 axis. 49 Tang and colleagues found that long noncoding RNA HOTAIR regulated autophagy through the miR-20b-5p/Atg7 axis in hepatic ischemia/reperfusion injury in the liver. 50 Study in breast cancer indicated that rutin restrained the growth and metastasis of mouse breast cancer cells by regulating the miRNA-129-1-3p-mediated calcium signaling pathway.…”

Identification of Two Long Non-Coding RNAs AC010082.1 and AC011443.1 as Biomarkers of Coronary Heart Disease Based on Logistic Stepwise Regression Prediction Model

“…Furthermore, miR-20b-5p plays an important role in mediating cardiomyocytes apoptosis via the HIF-1 α/NF- κ B pathway ( Zhou et al, 2020 ). And circHIPK3 acting as miR-20b-5p sponge could accelerate cardiomyocyte autophagy and apoptosis during myocardial I/R injury ( Qiu et al, 2021 ). Reportedly, miR-27a expression is upregulated in patients with CHD, and its expression level is remarkable correlated with the severity of coronary artery stenosis, which can be used as a biomarker of CHD ( Babaee et al, 2020 ).…”