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Lentivirus-Mediated Overexpression of miR-29a Promotes Axonal Regeneration and Functional Recovery in Experimental Spinal Cord Injury via PI3K/Akt/mTOR Pathway

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Abstract

MicroRNAs as a novel class of endogenous small non-coding RNAs, modulate negative gene expression at the post-transcriptional level. Our previous work has demonstrated that miR-29a reduces PTEN expression by directly targeting the 3′-UTRs (untranslated regions) of its mRNA, thus promoting neurite outgrowth. To further confirm the role of miR-29a in the recovery of SCI and its potential mechanisms, a recombinant lentiviral vector was used to promote miR-29a expression in the injured spinal cord. As compared with the LV-eGFP group and normal saline group, a significantly increased level of miR-29a expression and a markedly decreased level of PTEN expression were observed in the LV-miR-29a group. Overexpression of miR-29a increased the phosphorylation of two proteins (Akt and S6) of PI3K–AKT–mTOR signaling pathway and the expression of axonal regeneration associated key marker protein (neurofiament-200). Moreover, quantitative imaging analysis was performed to confirm that LV-miR-29a group expressed axonal regeneration at 4.0 ± 0.2-fold as much as the other two groups. Besides, miR-29a overexpression promoted hindlimb motor functional recovery. Collectively, these results suggested that miR-29a may be an important regulator for axon regeneration, and a potential therapeutic target for SCI recovery.

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Acknowledgements

This study was supported by the National Science Foundation of China (81471263), the Natural Science Foundation of Jiangsu Province (BK20151177), and Changzhou High-Level Medical Talents Training Project (2016ZCLJ005).

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Authors and Affiliations

  1. Department of Orthopedics, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China

    Hua Yin, Liming Shen, Chao Xu & Jinbo Liu

  2. Department of Orthopedics, The Jintan Affiliated Hospital of Jiangsu University, Jintan, 213200, Jiangsu, China

    Hua Yin

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  1. Hua Yin
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  2. Liming Shen
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  4. Jinbo Liu
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Correspondence to Jinbo Liu.

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Yin, H., Shen, L., Xu, C. et al. Lentivirus-Mediated Overexpression of miR-29a Promotes Axonal Regeneration and Functional Recovery in Experimental Spinal Cord Injury via PI3K/Akt/mTOR Pathway. Neurochem Res 43, 2038–2046 (2018). https://doi.org/10.1007/s11064-018-2625-5

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  • DOI: https://doi.org/10.1007/s11064-018-2625-5

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