Department of Cardiopulmonary Rehabilitation, The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang City, Liaoning Province, China.
Department of Research Administration, The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang City, Liaoning Province, China.
Bioengineered. 2022 May;13(5):13141-13149. doi: 10.1080/21655979.2022.2059862.
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.
自噬相关环状 RNA (ACR) 已被报道可保护心肌组织免受损伤并参与慢性心力衰竭 (CHF)，但其在 CHF 中的作用尚不清楚。本研究旨在研究 ACR 在 CHF 中的作用。通过 RT-qPCR 分析 CHF（缺血性，n=60）患者和健康对照者（n=60）的 ACR 和 miR-532 水平。通过生存曲线分析评估 ACR 的预后价值。在心肌细胞中过表达 ACR，并通过 RT-qPCR 和甲基化特异性 PCR（MSP）分析 ACR 过表达对 miR-532 表达和 miR-532 基因甲基化的影响。用细胞凋亡测定分析缺氧条件下心肌细胞的凋亡。结果观察到 ACR 在 CHF 中表达下调。Kaplan-Meier 和多变量 Cox 回归分析表明，低 ACR 预测 CHF 患者的总生存率，并且 ACR 与血浆样本中的 miR-532 呈负相关。在心肌细胞中，ACR 增加 miR-532 基因甲基化以降低其表达。细胞凋亡分析表明，ACR 过表达可降低 miR-532 过表达对缺氧条件下心肌细胞凋亡的增强作用。因此，ACR 在 CHF 中下调，并且可能通过甲基化下调 miR-532 来抑制缺氧诱导的心肌细胞凋亡。
