LncRNA 2810403D21Rik/Mirf promotes ischemic myocardial injury by regulating autophagy through targeting Mir26a
Authors: Xiaomin Su
Haihai Liang
Rui Yang
Jian Sun
Lu Zhang
Xuelian Li
Yuhong Zhou
Lifang Lv
Xiaoguang Zhao
Qiuxia Wu
He Yan
Hongli Shan
Tong Yu
Zhimin Du
Huitong Shan
Journal: Autophagy (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Autophagy; Mir26a; Usp15; lncRNA-2810403D21Rik/Mirf; myocardial infarction.
Affiliations: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University , Harbin, Heilongjiang, P. R. China., Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University , Harbin, Heilongjiang, P. R. China., Institute of Clinical Pharmacy, The 2nd Affiliated Hospital, Harbin Medical University , Harbin, Heilongjiang, P. R. China.

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: 3-MA: 3-methyladenine; AAV-9: adenovirus associated virus-9; agoMir26a: cholesterol-conjugated Mir26a mimic; AMI: acute myocardial infarction; AMO-26a: Mir26a inhibitor; ATG: autophagy related; BECN1: beclin 1; ceRNA: competitive endogenous RNAs; EF: ejection fraction; f-2810403D21Rik/Mirf: fragment encompassing the Mir26a binding site; FS: fraction shortening; GFP-mRFP: a plasmid expressing green fluorescent protein-monomeric red fluorescent protein; lncRNA: long non-coding RNA; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; Mirf: myocardial infarction-regulatory factor; miRNAs: microRNAs; NC: negative control; NMCMs: neonatal mice cardiomyocytes; shRNA: short hairpin RNA; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; Usp15: ubiquitin specific peptidase 15. 

Retracted: No

PubPeer comments:
 Could the authors explain the identical sequence of primers for the microRNA 503 in mice in another paper? ![file] , 
 #1 Thanks for your comments on our paper. Having double-checked our primer ordering records, we found that the Mir-26a RT primer sequence is correct. The sequence repeated with another paper is the stem loop structure used for microRNA reverse transcription primer. The next few bases u201cAGCCTATu201d are specific for miR-26a. However, we also found that we wrote the F and R primers of miR-26a wrong in the paper, and the correct primer sequence is as follows. Mm-Mir26a-F GCGGTTCAAGTAATCCAGG Mm-Mir26a-R TGTCGTGGAGTCGGCAATT We kept our primer ordering records at that time, which confirmed that our data and conclusion are correct. We would like to expression our sincere and serious apology to you and to the journal for the accidental mistake and any inconvenience the mistake may cause. ,