Abstract
Objective: Ischaemic stroke has a high death rate and frequently results in long-term and severe
brain damage in survivors. miRNA-124-3p (miR-124-3p) treatment has been suggested
to reduce ischaemia and play a vital function in avoiding neuron death. An investigation
of the role of miR-124-3p, in the ischaemia damage repair or protection in the middle
cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation/reperfusion
(OGD/R) model, was the purpose of this research. Methods: The expression of miRNA and mRNA in the MCAO model was predicted using bioinformatics
analysis. The OGD/R neuronal model was developed. We examined the influence of a number
of compounds on the OGD/R model in vitro using gain- and loss-of-function approaches.
Results: For starters, miR-124-3p and Nrep level in the MCAO model were found to be lower
in the model predicted by bioinformatics than in the sham-operated group. And then
in the OGD/R model, miR-124-3p treatment reduced OGD/R neuronal damage, increased
neuronal survival, and reduced apoptosis in cell lines. Moreover, we further looked
at the impact of miR-124-3p on downstream Rnf38 and Nrep using the OGD/R model. Western
blot analysis and dual-luciferase reporter assays indicated that miR-124-3p binds
and inhibits Rnf38. Finally, although Nrep expression was reduced in the OGD/R model
neuronal model, it was shown that miR-124-3p administration reduced apoptosis and
increased neuronal activity, particularly with regard to axon regeneration-related
proteins. Conclusion: Our studies have shown that miR-124-3p may reduce neuronal injury by preventing Rnf38-mediated
effects on the Nrep axis.
Key Words
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Article info
Publication history
Published online: December 17, 2022
Accepted:
December 12,
2022
Received in revised form:
December 11,
2022
Received:
August 11,
2022
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106949
Copyright
© 2022 Elsevier Inc. All rights reserved.
