Research Paper Volume 13, Issue 8 pp 11528—11541
MicroRNA-532-5p protects against cerebral ischemia-reperfusion injury by directly targeting CXCL1
- 1 Department of Neurology and Central Laboratory, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng 224001, Jiangsu, China
- 2 Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, Jiangsu, China
- 3 Department of Central Laboratory, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng 224001, Jiangsu, China
Received: November 28, 2020 Accepted: March 14, 2021 Published: April 18, 2021https://doi.org/10.18632/aging.202846
How to Cite
Copyright: © 2021 Shi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
We investigated the function of microRNA (miR)-532-5p in cerebral ischemia-reperfusion injury (CI/RI) and the underlying mechanisms using oxygen-glucose deprivation and reperfusion (OGD/R)-treated SH-SY5Y cells and middle cerebral artery occlusion (MCAO) model rats. MiR-532-5p levels were significantly downregulated in OGD/R-treated SH-SY5Y cells and the brain tissues of MCAO model rats. MiR-532-5p overexpression significantly reduced apoptosis, reactive oxygen species (ROS), and inflammation in the OGD/R-induced SH-SY5Y cells. Bioinformatics analysis using the targetscan and miRDB databases as well as dual luciferase reporter assays confirmed that miR-532-5p directly binds to the 3’UTR of C-X-C Motif Ligand 1 (CXCL1). Methylation-specific PCR (MSP) analysis showed that miR-532-5p expression was reduced in OGD/R-treated SH-SY5Y cells because of miR-532-5p promoter hypermethylation. Moreover, 5-azacytidine, a methylation inhibitor, restored miR-532-5p expression in OGD/R-treated SH-SY5Y cells. Brain tissues of MCAO model rats showed significantly increased cerebral infarction areas, cerebral water, neuronal apoptosis, and activated CXCL1/CXCR2/NF-κB signaling, but these effects were alleviated by intraventricular injection of miR-532-5p agomir. These findings demonstrate that miR-532-5p overexpression significantly reduces in vitro and in vivo CI/RI by targeting CXCL1. Thus, miR-532-5p is a potential therapeutic target for patients with CI/RI.