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MiR-361-5p promotes oxygen–glucose deprivation/re-oxygenation induced neuronal injury by negatively regulating SQSTM1 in vitro

Abstract

It has been reported that microRNAs (miRNAs) play essential roles in cerebral ischemia and reperfusion (I/R) injury. This study aimed to explore the role of miR-361-5p in oxygen–glucose deprivation/re-oxygenation-induced neuronal injury in vitro. Cerebral I/R injury cell model was established by using PC12 cells exposed to oxygen–glucose deprivation/re-oxygenation (OGD/R). The expression of miR-361-5p and SQSTM1 was evaluated by qRT-PCR or western blot. Neuronal apoptosis was detected by flow cytometry, and cell viability was assessed by CCK-8 assay. The effects of miR-361-5p on the release of LDH and the levels of MDA, SOD, and GSH-Px were investigated by respective detection kits. Dual-luciferase reporter assay and RIP assay were performed to determine the interaction between miR-361-5p and SQSTM1. Rescue experiments were performed to evaluate the function of miR-361-5p and SQSTM1. MiR-361-5p was significantly upregulated, and SQSTM1 was significantly downregulated in OGD/R-stimulated PC12 cells. MiR-361-5p could directly interact with SQSTM1 and negatively regulated it. Inhibition of miR-361-5p efficiently inhibited OGD/R-induced apoptosis and attenuated OGD/R-induced growth defect in PC12 cells. In addition, SQSTM1 overexpression partially attenuates the apoptosis and promoted the viability of OGD/R-treated PC12 cells, which were aggravated by miR-361-5p mimics. Our study demonstrated that miR-361-5p promotes OGD/R-induced neuronal injury via regulating SQSTM1 in PC12 cells.

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Data availability

The data are not publicly available due to their containing information that could compromise the privacy of research participants, but are available on request from the corresponding author.

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Acknowledgements

We thank Science and Technology Project of Guangdong Province for approving.

Funding

This work was supported by the Science and Technology Project of Guangdong Province (2018KJYZ026).

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TZ: study concepts, literature research, clinical studies, data analysis, experimental studies, manuscript writing and review; SZ: study design, literature research, experimental studies, and manuscript editing; YH: definition of intellectual content, clinical studies, data acquisition and statistical analysis; ZL: data acquisition, manuscript preparation and data analysis; QC: data acquisition and statistical analysis. All authors have read and approved the submission of the manuscript.

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Correspondence to Tao Zeng.

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Zeng, T., Zhang, S., He, Y. et al. MiR-361-5p promotes oxygen–glucose deprivation/re-oxygenation induced neuronal injury by negatively regulating SQSTM1 in vitro. Metab Brain Dis 36, 2359–2368 (2021). https://doi.org/10.1007/s11011-021-00845-x

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Keywords

  • MiR-361-5p
  • SQSTM1
  • Apoptosis
  • Oxygen–glucose deprivation/re-oxygenation