期刊
AUTOPHAGY
卷 16, 期 6, 页码 1077-1091出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2019.1659610
关键词
Autophagy; Mirf; Mir26a; myocardial infarction; Usp15
类别
资金
- National Natural Science Foundation of China [81770284, 31671187, 81673425]
More evidence is emerging of the roles long non-coding RNAs (lncRNAs) play as regulatory factors in a variety of biological processes, but the mechanisms underlying the function of lncRNAs in acute myocardial infarction (AMI) have not been explicitly delineated. The present study identified the lncRNA 2810403D21Rik/AK007586/Mirf (myocardial infarction-regulatory factor), that inhibited macroautophagy/autophagy by modulating Mir26a (microRNA 26a). Inhibition of Mir26a led to cardiac injury both in vitro and in vivo, whereas overexpression of Mir26a attenuated ischemic stress-induced cell death by activating autophagy through targeting Usp15 (ubiquitin specific peptidase 15). More importantly, 2810403D21Rik/Mirf acted as a competitive endogenous RNA (ceRNA) of Mir26a; forced expression of 2810403D21Rik/Mirf downregulated Mir26a to inhibit autophagy. In contrast, loss of 2810403D21Rik/Mirf resulted in upregulation of Mir26a to promote autophagy and alleviate cardiac injury, which in turn improved cardiac function in MI mice. This study identified a lncRNA 2810403D21Rik/Mirf that functions as an anti-autophagic molecule via ceRNA activity toward Mir26a. Our findings suggest that knockdown of 2810403D21Rik/Mirf might be a novel therapeutic approach for cardiac diseases associated with autophagy.
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