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Potential Mechanism of Neurite Outgrowth Enhanced by Electrical Stimulation: Involvement of MicroRNA-363-5p Targeting DCLK1 Expression in Rat

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Abstract

Electrical stimulation (ES) promotes neurite outgrowth and nerve regeneration, but the underlying mechanisms remain undefined. In the present study, we investigated the role of micro RNAs (miRNAs) in ES-mediated neurite outgrowth. First, we performed microarray analyses to identify changes in the miRNAs profile of dorsal root ganglion neurons (DRGNs) following ES. The expression of 16 known miRNAs was altered by ES. Bioinformatics showed that the potential targets of these differentially expressed miRNAs were involved in neurite outgrowth. We focused on miRNA-363-5p (miR-363-5p), because its expression was consistently altered by ES in the present study. Silencing miR-363-5p promoted neurite outgrowth, while miR-363-5p mimic reduced neurite outgrowth. Downregulation of miR-363-5p indicated that double cortin-like kinase (DCLK) 1, a major microtubule-associated protein, was a direct target of miR-363-5p in DRGNs. Knockdown of DCLK1 recapitulated the beneficial effect of a miR-363-5p inhibitor on DRG neurite outgrowth. In conclusion, our data has indicated that miR-363-5p is involved in ES-promoted neurite outgrowth by targeting DCLK1. These findings provide new insights into the roles of miRNAs in ES-enhanced neurite outgrowth and regeneration.

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Acknowledgements

This study was funded by grants from the National Natural Science Foundation of China (81201389 and 81371947), the National Basic Research Program of China (973 Program No. 2014CB542206), the Program for Changjiang Scholar and Innovative Research Team in University (IRT-14R08 and IRT13051), and A Foundation for the Author of National Excellent Doctoral Dissertation of PR China (No.201480). Funding for open access was received from the National Natural Science Foundation of China. We thank Lan Lifeng and Fan Jing for their excellent technical assistance.

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Authors and Affiliations

  1. Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

    Xin Quan, Liangliang Huang, Yafeng Yang, Teng Ma, Zhongyang Liu, Jun Ge, Jinghui Huang & Zhuojing Luo

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  1. Xin Quan
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  2. Liangliang Huang
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Correspondence to Jinghui Huang or Zhuojing Luo.

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Quan, X., Huang, L., Yang, Y. et al. Potential Mechanism of Neurite Outgrowth Enhanced by Electrical Stimulation: Involvement of MicroRNA-363-5p Targeting DCLK1 Expression in Rat. Neurochem Res 42, 513–525 (2017). https://doi.org/10.1007/s11064-016-2100-0

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