Downregulation of autophagy-related circular RNA (ACR) is correlated with poor survival of patients with chronic heart failure

自噬相关环状 RNA (ACR) 的下调与慢性心力衰竭患者生存率低有关

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作者:Haihui Yan, Dan Du, Chen Wang, Miao Tian

Abstract

Autophagy-related circular RNA (ACR) has been reported to protect myocardial tissues from injury and participate in chronic heart failure (CHF), while its role in CHF is unknown. This study aimed to study the role of ACR in CHF. ACR and miR-532 levels in CHF (ischemic-origin, n = 60) patients and healthy controls (n = 60) were analyzed by RT-qPCR. The prognostic value of ACR was analyzed by survival curve analysis. ACR was overexpressed in cardiomyocytes, and the effects of ACR overexpression on the expression of miR-532 and the methylation of miR-532 gene were analyzed using RT-qPCR and methylation-specific PCR (MSP). Cardiomyocyte apoptosis under hypoxic conditions was analyzed with cell apoptosis assay. It was observed that ACR expression was downregulated in CHF. Kaplan‑Meier and multivariate Cox regression analysis suggested that low ACR predicted overall survival of CHF patients and ACR was inversely correlated with miR-532 across plasma samples. In cardiomyocytes, ACR increased miR-532 gene methylation to decrease its expression. Cell apoptosis analysis showed that ACR overexpression reduced the enhancing effects of miR-532 overexpression on cardiomyocyte apoptosis under hypoxic conditions. Therefore, ACR is downregulated in CHF and may suppress hypoxia-induced cardiomyocytes by downregulating miR-532 via methylation.

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