The Circular RNA ACR Attenuates Myocardial Ischemia/reperfusion Injury by Suppressing Autophagy Via Modulation of the Pink1/ FAM65B Pathway

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2018 Oct 24

PMID 30349076

Citations 126

Authors

Lu-Yu Zhou

Mei Zhai

Yan Huang

Sheng Xu

Tao An

Yun-Hong Wang

Rong-Cheng Zhang

Cui-Yun Liu

Yan-Han Dong

Man Wang

Li-Li Qian

Murugavel Ponnusamy

Yu-Hui Zhang

Jian Zhang

Kun Wang

Affiliations

Soon will be listed here.

Abstract

Dysregulated autophagy is associated with many pathological disorders such as cardiovascular diseases. Emerging evidence has suggested that circular RNAs (circRNAs) have important roles in some biological processes. However, it remains unclear whether circRNAs participate in the regulation of autophagy. Here we report that a circRNA, termed autophagy-related circular RNA (ACR), represses autophagy and myocardial infarction by targeting Pink1-mediated phosphorylation of FAM65B. ACR attenuates autophagy and cell death in cardiomyocytes. Moreover, ACR protects the heart from ischemia/reperfusion (I/R) injury and reduces myocardial infarct sizes. We identify Pink1 as an ACR target to mediate the function of ACR in cardiomyocyte autophagy. ACR activates Pink1 expression through directly binding to Dnmt3B and blocking Dnmt3B-mediated DNA methylation of Pink1 promoter. Pink1 suppresses autophagy and Pink1 transgenic mice show reduced myocardial infarction sizes. Further, we find that FAM65B is a downstream target of Pink1 and Pink1 phosphorylates FAM65B at serine 46. Phosphorylated FAM65B inhibits autophagy and cell death in the heart. Our findings reveal a novel role for the circRNA in regulating autophagy and ACR-Pink1-FAM65B axis as a regulator of autophagy in the heart will be potential therapeutic targets in treatment of cardiovascular diseases.

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