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

  • Author Footnotes
    1 Peng Huang and Songren Wei equally contributed to this article.
    Peng Huang
    Footnotes
    1 Peng Huang and Songren Wei equally contributed to this article.
    Affiliations
    Women and Children Medical Research Center, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan 528000, China

    Surgical Department, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan 528000, China
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  • Author Footnotes
    1 Peng Huang and Songren Wei equally contributed to this article.
    Songren Wei
    Footnotes
    1 Peng Huang and Songren Wei equally contributed to this article.
    Affiliations
    Department of Neuropharmacology and Novel Drug Discovery, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
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  • Jing Ren
    Affiliations
    The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
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  • Zhuohong Tang
    Affiliations
    Department of Pharmacy, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan 528000, China
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  • Mingjuan Guo
    Affiliations
    Women and Children Medical Research Center, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan 528000, China
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  • Fen Situ
    Affiliations
    Surgical Department, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan 528000, China
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  • Dan Zhang
    Affiliations
    Surgical Department, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan 528000, China
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  • Jianghua Zhu
    Affiliations
    Department of Pharmacy, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan 528000, China
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  • Li Xiao
    Correspondence
    Corresponding authors.
    Affiliations
    Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan 528000, China
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  • Jiangping Xu
    Correspondence
    Corresponding authors.
    Affiliations
    Department of Neuropharmacology and Novel Drug Discovery, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
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  • Guoqing Liu
    Correspondence
    Corresponding authors.
    Affiliations
    Women and Children Medical Research Center, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan 528000, China
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  • Author Footnotes
    1 Peng Huang and Songren Wei equally contributed to this article.

      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.

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