Abstract
Ischemic stroke is a nervous system disease with high rates of disability and mortality. MicroRNAs have been reported to modulate cerebral ischemia. The current study aimed to study the role of miR-361-3p in cerebral ischemia–reperfusion (I/R) injury. Experimental results revealed that miR-361-3p level was downregulated in a middle cerebral artery occlusion-induced ischemic stroke mouse model and in oxygen–glucose deprivation/reoxygenation-stimulated SH-SY5Y cells. After overexpressing miR-361-3p, the percentage of brain infarct volume and neurobehavioral scores in mice were significantly reduced, and the neuronal apoptosis was inhibited. Moreover, miR-361-3p overexpression could limit the production of reactive oxygen species (ROS). Furthermore, we investigated the underlying molecular mechanisms of miR-361-3p and identified that miR-361-3p combined with NACC1 3ʹUTR to negatively modulate its expression. In addition, NACC1 interacts with the PINK1/Parkin pathway in neurons. NACC1 overexpression could rescue the impacts of miR-361-3p mimics on cell apoptosis, ROS production and the PINK1/Parkin pathway. In conclusion, miR-361-3p could improve ischemia brain injury by targeting NACC1 through the PINK1/Parkin pathway. Therefore, miR-361-3p may serve as a potential therapeutic target for the brain injury after I/R.
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This worked was supported by National Natural Science Foundation of China (No. 81401030) and Health Commission of Hubei Province scientific research project (No. WJ2021F114, WJ2021M181).
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Ye, X., Song, H., Hu, H. et al. MiR-361-3p alleviates cerebral ischemia–reperfusion injury by targeting NACC1 through the PINK1/Parkin pathway. J Mol Histol 53, 357–367 (2022). https://doi.org/10.1007/s10735-021-10049-3
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DOI: https://doi.org/10.1007/s10735-021-10049-3