Abstract |
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. ABBREVIATIONS:
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Authors | Haihai Liang, Xiaomin Su, Qiuxia Wu, Huitong Shan, Lifang Lv, Tong Yu, Xiaoguang Zhao, Jian Sun, Rui Yang, Lu Zhang, He Yan, Yuhong Zhou, Xuelian Li, Zhimin Du, Hongli Shan |
Journal | Autophagy
(Autophagy)
Vol. 16
Issue 6
Pg. 1077-1091
(06 2020)
ISSN: 1554-8635 [Electronic] United States |
PMID | 31512556
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- MicroRNAs
- Mirn26 microRNA, mouse
- RNA, Long Noncoding
- Hydrogen Peroxide
- Ubiquitin-Specific Proteases
- Usp15 protein, mouse
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Topics |
- Animals
- Autophagosomes
(drug effects, genetics, metabolism, ultrastructure)
- Autophagy
(drug effects, genetics)
- Cell Survival
(drug effects)
- Gene Knockdown Techniques
- Gene Silencing
- HEK293 Cells
- Humans
- Hydrogen Peroxide
(toxicity)
- Mice
- Mice, Inbred C57BL
- MicroRNAs
(genetics, metabolism)
- Microscopy, Electron, Transmission
- Mutation
- Myocardial Infarction
(genetics, metabolism, pathology)
- Myocytes, Cardiac
(drug effects, metabolism)
- RNA, Long Noncoding
(genetics, metabolism)
- Ubiquitin-Specific Proteases
(genetics, metabolism)
- Up-Regulation
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