LncAABR07025387.1 Enhances Myocardial Ischemia/Reperfusion Injury Via miR-205/ACSL4-Mediated Ferroptosis.

Abstract

Ferroptosis is associated with the pathology of myocardial ischemia/reperfusion (MI/R) injury following myocardial infarction, which is a leading cause of death worldwide. Although long noncoding RNAs (lncRNAs) are known to regulate gene expression, their roles in MI/R-induced ferroptosis remain unclear. In this study, we explored the lncRNA expression profiles in a rat model of MI/R injury and found that the novel lncRNA, lncAABR07025387.1, was highly expressed in MI/R-injured myocardial tissues and hypoxia/reoxygenation (H/R)-challenged myocardial cells. Silencing lncAABR07025387.1 improved MI/R injury in vivo and inhibited myocardial cell ferroptosis under H/R conditions. Bioinformatics analyses and luciferase, pull-down, and RNA-binding immunoprecipitation assays further revealed that lncAABR07025387.1 interacted with miR-205, which directly targeted ACSL4, a known contributor to ferroptosis. Furthermore, downregulating miR-205 reversed the ACSL4 inhibition induced by silencing lncAABR07025387.1. These findings suggest that, mechanistically, lncAABR07025387.1 negatively regulates miR-205 expression and subsequently upregulates ACSL4-mediated ferroptosis. In conclusion, this study demonstrates that lncAABR07025387.1 acts as a competing endogenous RNA during MI/R injury and highlights the therapeutic potential of lncRNAs for treating myocardial injury.

• Authors: Weixin Sun, Xiang Wu, Peng Yu, Qian Zhang, Le Shen, Jiandong Chen, Huaqin Tong, Manlu Fan, Haibo Shi, Xiaohu Chen
• Journal: Frontiers in cell and developmental biology (Front Cell Dev Biol) Vol. 10 Pg. 672391 ( 2022) ISSN: 2296-634X [Print] Switzerland
• PMID: 35186915 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Sun, Wu, Yu, Zhang, Shen, Chen, Tong, Fan, Shi and Chen.