Circ-HIPK2 Accelerates Cell Apoptosis and Autophagy in Myocardial Oxidative Injury by Sponging miR-485-5p and Targeting ATG101

Abstract: Myocardial injury has been deemed as a major cause of heart diseases including myocarditis and coronary heart disease, which have brought multiple mortalities globally. Long non-coding RNAs (lncRNAs) are widely recognized in diverse diseases. However, the role of circular RNA HIPK2 (circ-HIPK2) remains unclear in myocardial injury induced by H 2 O 2 . We attempted to investigate the probable role of circ-HIPK2 in myocardial injury induced by H 2 O 2 . This study discovered that the treatment of H 2 O 2 inhibited cell proliferation but boosted cell apoptosis and autophagy. ATG101 was upregulated in primary mouse neonatal cardiomyocytes under H 2 O 2 treatment. ATG101 knockdown promoted proliferation and limited apoptosis by attenuating autophagy in H 2 O 2 -injured mouse neonatal cardiomyocytes. Furthermore, miR-485-5p was validated to combine with ATG101 and circ-HIPK2, and circ-HIPK2 positively regulated ATG101 expression by sponging miR-485-5p. At last, silenced circ-HIPK2 mediated the promotion of cell proliferation, and repression of cell apoptosis was restored by ATG101 amplification. In a word, circ-HIPK2 facilitates autophagy to accelerate cell apoptosis and cell death in H 2 O 2 -caused myocardial oxidative injury through the miR-485-5p/ATG101 pathway, indicating a novel therapeutic target point for patients with myocardial injury.