Circ_ZNF512-Mediated miR-181d-5p Inhibition Limits Cardiomyocyte Autophagy and Promotes Myocardial Ischemia/Reperfusion Injury through an EGR1/mTORC1/TFEB-Based Mechanism
Chen Huang, Liliang Shu, Hualu Zhang, Xiaohua Zhu, Gongcheng Huang, Jing Xu
Abstract
Studies have shown that circRNAs are important regulatory molecules involved in cell physiology and pathology. Herein, we analyzed the role of circ_ZNF512 in cardiomyocyte autophagy of myocardial ischemia/reperfusion (I/R) injury. A mouse model was induced by ligation of the left anterior descending artery followed by reperfusion. An in vitro model was also developed in cultured cardiomyocytes following hypoxia/reoxygenation (H/R) injury. It was established that EGR1 expression was increased in myocardial tissues of I/R mice and H/R-induced cardiomyocytes. Silencing of circ_ZNF512 attenuated its binding to miR-181d-5p, which in turn impaired the EGR1 expression by targeting its 3′-UTR, thus promoting the autophagy of cardiomyocytes and suppressing cell apoptosis to alleviate myocardial tissue injury. Additionally, the circ_ZNF512/miR-181d-5p/EGR1 crosstalk activated the mTORC1/TFEB signaling pathway, increasing mTORC1 expression while suppressing TFEB expression. Together, circ_ZNF512 knockdown protects against myocardial I/R injury, which may be a potential therapeutic approach for preventing myocardial I/R injury.