Silencing circular RNA circ_0010729 protects human cardiomyocytes from oxygen-glucose deprivation-induced injury by up-regulating microRNA-145-5p

沉默环状 RNA circ_0010729 可通过上调 microRNA-145-5p 保护人类心肌细胞免受氧葡萄糖缺乏引起的损伤

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作者:Qifeng Jin, Yuanyuan Chen

Abstract

Circular RNAs (circRNAs) are effector molecules that exert functions in cardiovascular diseases. Nevertheless, the effects of circRNAs on myocardial ischemia remain uninvestigated. This paper aimed to explore the functions of circ_0010729 in oxygen-glucose-deprivation (OGD)-caused injury of human cardiomyocytes (HCM). HCM were exposed to OGD environment for 4 h. Then the expression of circ_0010729 was evaluated by RT-qPCR. After transfection, cell viability, apoptosis, and migration were examined to evaluate the impact of overexpression and knockdown of circ_0010729 on OGD-induced cell injury. The regulation between circ_0010729 and microRNA-145-5p (miR-145-5p) was verified. After miR-145-5p inhibitor transfection, whether aberrant miR-145-5p expression affected the modulation of circ_0010729 in OGD-induced cell injury was measured. Western blot was utilized to analyze mTOR and MEK/ERK pathway-related proteins. OGD treatment enhanced circ_0010729 expression and evoked cell injury in HCM. Moreover, OGD-induced injury was aggrandized by circ_0010729 overexpression via suppressing cell growth and migration in HCM. Knockdown of circ_0010729 attenuated OGD-induced injury. In addition, circ_0010729 negatively regulated miR-145-5p expression. MiR-145-5p inhibition reversed the effects of silencing circ_0010729 on OGD-induced injury and mTOR and MEK/ERK pathways. We demonstrated that silencing circ_0010729 activated mTOR and MEK/ERK pathways by up-regulating miR-145-5p, thereby protecting HCM from OGD-induced injury.

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