MicroRNA-124-3p alleviates cerebral ischaemia-induced neuroaxonal damage by enhancing Nrep expression

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 sur-vival, 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.

Automated summary

The objective of this study was to investigate the role of miR-124-3p in ischaemic stroke. It was found that the levels of miR-124-3p and Nrep were decreased in the MCAO model predicted by bioinformatics. In the OGD/R model, miR-124-3p treatment reduced neuronal damage, increased survival, and inhibited apoptosis. Further analysis revealed that miR-124-3p bound and inhibited Rnf38, which was involved in the Nrep axis. Overall, miR-124-3p may have potential therapeutic effects in reducing neuronal injury.