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miR-181a targets PTEN to mediate the neuronal injury caused by oxygen-glucose deprivation and reoxygenation

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Abstract

Evidence suggests that the microRNA-181 (miR-181) family performs various roles in the pathophysiology of cerebral ischemia and reperfusion injury (CIRI). MiR-181a has been identified as a critical determinant of neuronal survival. Moreover, the significance of miR-181a in controlling neuronal death after CIRI has received little attention. The objective of this study was to assess the role of miR-181a in neuronal cell injury after CIRI. To mimic the in-vitro and in-vivo CIRI, we developed an oxygen-glucose deficiency/reoxygenation (OGD/R) model in SH-SY5Y cells and a transient middle cerebral artery occlusion model in rats. MiR-181a expression was significantly higher in both in-vivo and in-vitro CIRI models. The overexpression of miR-181a increased cell damage and oxidative stress caused by OGD/R, whereas inhibition of miR-181a reduced both. PTEN has also been found to be a direct miR-181a target. PTEN overexpression reduced cell apoptosis and oxidative stress induced by miR-181a upregulation under an OGD/R condition. Furthermore, we found that the rs322931 A allele was related to increased miR-181a levels in IS peripheral blood and higher susceptibility to IS. The current results offer new insights into the understanding of the molecular pathophysiology of CIRI, as well as possible new treatment candidates.

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Data availability

The datasets used in this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We’d like to thank MJEditor (www.mjeditor.com) for its linguistic assistance during the prepare of this manuscript. We also thank the participants in this study.

Funding

This work was supported by funding from the National Nature Science Foundation of China (grant numbers 81571157, 81300929 and 81670252) and the Natural Science Foundation of Guangdong Province (grant numbers 2019A1515011424 and 2023A1515012750), the Youth Cultivation Foundation (grant number GDMUQ2021006) and One Hundred Youth Research Projects (grant number GDMUD2022010) of Guangdong Medical University, the Medical Scientific Research Foundation of Guangdong Province, China (grant number: A2023193 and A2022139) and the Non-funded Science and Technology Research Foundation of Zhanjiang City (grant number: 2021B01370).

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Author notes

  1. Shengnan Li, Peiyi Zhu and Yajun Wang contributed equally to this work.

Authors and Affiliations

  1. Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China

    Shengnan Li, Peiyi Zhu, Shaoting Huang, Zhaochun Wu, Jiawen He, Xingjuan Hu, Ying Wang, Yanquan Yuan, Bin Zhao & You Li

  2. Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China

    Shengnan Li, Peiyi Zhu, Shaoting Huang, Zhaochun Wu, Jiawen He, Xingjuan Hu, Ying Wang, Yanquan Yuan, Bin Zhao & You Li

  3. Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China

    Shengnan Li, Shaoting Huang, Bin Zhao & You Li

  4. Shunde Maternal and Children’s Hospital, Maternal and Children’s Health Research Institute, Guangdong Medical University, Shunde, 528300, China

    Yajun Wang & Guoda Ma

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  1. Shengnan Li
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Contributions

Study design were performed by Y.L. and G.M.; Material preparation and data collection were performed by S.L., P.Z. and Y.W.; Data analysis were finished by X.H., Y.W., Z.W., S.H., J.H. and Y.Y.; The first draft was edited by B.Z.; All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Guoda Ma or You Li.

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Research involving human participants and/or animals

This study was performed in line with the principles of the Declaration of Helsinki. This study was approved via the Ethics Committee of the Affiliated Hospital of Guangdong Medical University and the animal ethics committee of Guangdong Medical University.

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The letter of informed consent was gained from each participant prior to investigation enlistment.

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The authors confirm that informed consent was obtained from the human study participants for publication of the data involved in this study.

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Li, S., Zhu, P., Wang, Y. et al. miR-181a targets PTEN to mediate the neuronal injury caused by oxygen-glucose deprivation and reoxygenation. Metab Brain Dis 38, 2077–2091 (2023). https://doi.org/10.1007/s11011-023-01219-1

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