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The Long Non-coding RNA SNHG12 Functions as a Competing Endogenous RNA to Modulate the Progression of Cerebral Ischemia/Reperfusion Injury

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Abstract

Increasing research has proved that long non-coding RNAs (lncRNAs) play a critical role in a variety of biological processes. However, their functions in cerebral ischemia are still unclear. We found that the small nucleolar RNA host gene 12 (SNHG12) is a new type of lncRNA induced by ischemia/reperfusion. Here, we show that the expression of SNHG12 was upregulated in the brain tissue of mice exposed to middle cerebral artery occlusion/reperfusion (MCAO/R) and primary mouse cerebral cortex neurons treated with oxygen-glucose deprivation/reoxygenation (OGD/R). Mechanistically, SNHG12 knockdown resulted in larger infarct sizes and worse neurological scores in MCAO/R mice. Consistent with the in vivo results, SNHG12 upregulation significantly increased the viability and prevented apoptosis of neurons cultured under OGD/R conditions. In addition, we found that SNHG12 acts as a competing endogenous RNA (ceRNA) with microRNA (miR)-136-5p, thereby regulating the inhibition of its endogenous target Bcl-2. Moreover, SNHG12 was proven to target miR-136-5p, increasing Bcl-2 expression, which finally led to the activation of PI3K/AKT signaling. In conclusion, we demonstrated that SNHG12 acts as a ceRNA of miR-136-5p, thereby targets and regulates the expression of Bcl-2, which attenuates cerebral ischemia/reperfusion injury via activation of the PI3K/AKT pathway. This knowledge helps to better understand the pathophysiology of cerebral ischemic stroke and may provide new treatment options for this disease.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

We would like to thank Institute of Biomedical and Pharmaceutical Sciences of Guangdong University of Technology for invaluable assistance in conducting these experiments, and the other members of the research group for useful discussion in preparing this manuscript.

Funding

This study was supported by the China Postdoctoral Science Foundation (2019M652826), Guangdong Natural Science Foundation of China (2021A1515011064) and the National Natural Science Foundation of China (31601089).

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Authors and Affiliations

  1. Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China

    Hao Zhang, Meng Li & Xiaoou Sun

  2. Department of Pharmacy, The Third People’s Hospital of Kunming, Kunming, 650000, China

    Yuan Liu & Gongfeng Peng

  3. School of Life Science and Bioengineering, Henan University of Urban Construction, Pingdingshan, 467000, China

    Tao Zhu

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  1. Hao Zhang
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  2. Yuan Liu
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  3. Meng Li
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  5. Tao Zhu
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Contributions

Z.H. designed and performed the experiments, analyzed and interpreted the data, and wrote the manuscript. L.Y., L.M., Z.T. and P.G. helped with data collection and interpretation and contributed to critical manuscript revision. S.X. conceived the study, obtained funding, and critically revised the manuscript. All the authors participated in the experiment performance and data analysis. All authors read, revised, and approved the final manuscript.

Corresponding author

Correspondence to Xiaoou Sun.

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This experimental study was approved by the Animal Protection and Utilization Committee of the Guangdong Pharmaceutical University.

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Zhang, H., Liu, Y., Li, M. et al. The Long Non-coding RNA SNHG12 Functions as a Competing Endogenous RNA to Modulate the Progression of Cerebral Ischemia/Reperfusion Injury. Mol Neurobiol 59, 1073–1087 (2022). https://doi.org/10.1007/s12035-021-02648-8

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  • DOI: https://doi.org/10.1007/s12035-021-02648-8

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