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MiR-15a attenuates peripheral nerve injury-induced neuropathic pain by targeting AKT3 to regulate autophagy

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Abstract

Objective

Aim of this study was to detect the expression of miR-15a in rats following chronic constriction injury (CCI) and to investigate the regulatory functions of miR-15a during neuropathic pain (NP) development.

Methods

CCI was performed in adult Sprague–Dawley rats to set up the rat model of neuropathic pain. MiR-15a agomir and scrambled control were delivered into the implanted catheter of rats. The mechanical allodynia and thermal hyperalgesia were assessed in both CCI- and sham-operated groups. Rat lumbar spinal cord tissues were harvested for mRNA and protein analyses. The primary spinal microglia were isolated from adult Sprague–Dawley rats and transfected with miR-15a mimics, scramble miRNA, miR-15a inhibitor or its corresponding negative control. Cell lysates were collected for mRNA and protein analyses.

Results

Compared to sham-operated group, the expression of miR-15a in CCI rats was significantly reduced, whereas neuroinflammation in spinal cord tissues was increased. Intrathecal administration of miR-15a agomir significantly attenuated CCI-induced NP and the levels of proinflammatory cytokines, including IL-6, IL-1β, and TNF-α. AKT3 was predicted and confirmed as a miR-15a-regulated gene. We further demonstrated that miR-15a overexpression downregulated the level of AKT3 in primary rat microglia and rat CCI model. Moreover, the upregulation of miR-15a induced the expressions of autophagy-associated proteins, suggesting that the regulation mechanism of miR-15a in NP development involves AKT3-mediated autophagy via inhibiting the expression of AKT3.

Conclusion

Our findings indicated that miR-15a might serve as a promising therapeutic target for the management of NP through the stimulation of autophagic process.

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All data generated or analyzed during this study are included in this published article.

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Authors and Affiliations

  1. Department of Emergency, First Affiliated Hospital of Gannan Medical University, No. 23, Qingnian Road, Zhanggong District, Ganzhou, Jiangxi, China

    Longxue Cai, Xianfa Liu, Qicai Guo, Qi huang, Qiong Zhang & Zuohong Cao

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  1. Longxue Cai
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  2. Xianfa Liu
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  3. Qicai Guo
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  4. Qi huang
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  5. Qiong Zhang
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  6. Zuohong Cao
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Contributions

LXC and XFL conceived and designed the experiments, FL and QCG analyzed and interpreted the results of the experiments, QH, QZ and ZHC performed the experiments.

Corresponding author

Correspondence to Longxue Cai.

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Conflict of interest

Longxue Cai, Xianfa Liu, Qicai Guo, Qi huang, Qiong Zhang and Zuohong Cao declare that they have no conflict of interest.

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The animal use protocol listed below has been reviewed and approved by the Animal Ethical and Welfare Committee.

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Cai, L., Liu, X., Guo, Q. et al. MiR-15a attenuates peripheral nerve injury-induced neuropathic pain by targeting AKT3 to regulate autophagy. Genes Genom 42, 77–85 (2020). https://doi.org/10.1007/s13258-019-00881-z

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  • DOI: https://doi.org/10.1007/s13258-019-00881-z

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