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MiR-122 overexpression alleviates oxygen-glucose deprivation-induced neuronal injury by targeting sPLA2-IIA.

Authors :
Yu Y
Li P
Chen M
Zhan W
Zhu T
Min L
Liu H
Lv B
Source :
Frontiers in neurology [Front Neurol] 2024 May 10; Vol. 15, pp. 1395833. Date of Electronic Publication: 2024 May 10 (Print Publication: 2024).
Publication Year :
2024

Abstract

Background: Ischemic stroke (IS) is a neurological disease with significant disability and mortality. MicroRNAs were proven to be associated with cerebral ischemia. Previous studies have demonstrated miR-122 downregulation in both animal models of IS and the blood of IS patients. Nonetheless, the role and mechanism of miR-122-5p in IS remain unclear.<br />Methods: We established primary human and mouse astrocytes, along with HT22 mouse hippocampal neuronal cells, through oxygen-glucose deprivation/reoxygenation (OGD/R) treatment. To assess the impact of miR-122, we employed CCK8 assays, flow cytometry, RT-qPCR, western blotting, and ELISA to evaluate cell viability, apoptosis, reactive oxygen species (ROS) generation, and cytokine expression. A dual-luciferase reporter gene assay was employed to investigate the interaction between miR-122 and sPLA2-IIA.<br />Results: Overexpression of miR-122 resulted in decreased apoptosis, reduced cleaved caspase-3 expression, and increased cell viability in astrocytes and HT22 cells subjected to OGD/R. RT-qPCR and ELISA analyses demonstrated a decrease in mRNA and cytokine levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in both astrocytes and HT22 cells following miR-122 overexpression. Moreover, miR-122 overexpression reversed OGD/R-induced ROS levels and 8-OHdG formation in astrocytes. Additionally, miR-122 overexpression decreased the mRNA and protein expression of inducible nitric oxide synthase (iNOS). Furthermore, we found that miR-122 attaches to the 3'-UTR of sPLA2-IIA, thereby downregulate its expression.<br />Conclusion: Our study demonstrates that miR-122-mediated inhibition of sPLA2-IIA attenuates OGD/R-induced neuronal injury by suppressing apoptosis, alleviating post-ischemic inflammation, and reducing ROS production. Thus, the miR-122/sPLA2-IIA axis may represent a promising target for IS treatment.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2024 Yu, Li, Chen, Zhan, Zhu, Min, Liu and Lv.)

Details

Language :
English
ISSN :
1664-2295
Volume :
15
Database :
MEDLINE
Journal :
Frontiers in neurology
Publication Type :
Academic Journal
Accession number :
38798705
Full Text :
https://doi.org/10.3389/fneur.2024.1395833