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Downregulation of circAsxl2 Relieves Neuronal Injury Induced by oxygen-glucose deprivation/reperfusion

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Abstract

Background: Circular RNAs (circRNAs) have been shown to play an important role in cerebral ischemia-reperfusion (I/R) injury. However, the role of circAsxl2 (mmu_circ_0000346) in cerebral I/R injury remains unclear. Methods: Mouse brain neuronal cell line (HT-22) was used to perform oxygen-glucose deprivation/reperfusion (OGD/R) treatment. The levels of circAsxl2, microRNA (miR)-130b-5p and forkhead box O3 (FOXO3) were determined using quantitative real-time PCR. Cell viability and apoptosis were measured using cell counting kit 8 assay and flow cytometry. Commercial kits were used to assess cell cytotoxicity, inflammation and oxidative stress. Protein expression was analyzed by western blot. RNA interaction was verified using dual-luciferase reporter assay, RIP assay and RNA pull-down assay. Results: CircAsxl2 was highly expressed in OGD/R-induced HT-22 cells, and its silencing could alleviate OGD/R-induced apoptosis, inflammation and oxidative stress in HT-22 cells. MiR-130b-5p was sponged by circAsxl2, and its inhibitor could overturn the regulation of circAsxl2 knockdown on OGD/R-induced neuronal injury. FOXO3 was targeted by miR-130b-5p and its expression was positively regulated by circAsxl2. In addition, the regulation of circAsxl2 knockdown on OGD/R-induced neuronal injury also was reversed by FOXO3 overexpression. Conclusion: CircAsxl2/miR-130b-5p/FOXO3 axis accelerated OGD/R-induced neuronal injury, which might provide effective strategies for treating cerebral I/R injury.

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Acknowledgements

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Funding

This work was supported by General project of Natural Science Foundation of Hunan Province (No.2021JJ30528).

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  1. Wen Zhang and Dan Liu contributed equally to this work.

Authors and Affiliations

  1. Geriatrics Department, the First Hospital of Hunan University of Chinese Medicine, Changsha City, 410007, Hunan, China

    Wen Zhang

  2. Department of Rheumatology and Immunology, the First Hospital of Hunan University of Chinese Medicine, Changsha City, 410007, Hunan, China

    Dan Liu

  3. Medical innovation center, the First Hospital of Hunan University of Chinese Medicine, Changsha City, 410007, Hunan, China

    Jian Yi

  4. Department of cardiovascular diseases, the First Hospital of Hunan University of Chinese Medicine, No.95 Shaoshan middle road, Yuhua District, Changsha City, Hunan Province, China

    Jianmin Fan

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  1. Wen Zhang
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Contributions

Wen Zhang and Dan Liu designed and performed the research; Jian Yi, Jianmin Fan analyzed the data; Wen Zhang and Dan Liu wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jianmin Fan.

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Zhang, W., Liu, D., Yi, J. et al. Downregulation of circAsxl2 Relieves Neuronal Injury Induced by oxygen-glucose deprivation/reperfusion. Mol Neurobiol 61, 812–820 (2024). https://doi.org/10.1007/s12035-023-03532-3

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  • DOI: https://doi.org/10.1007/s12035-023-03532-3

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