MiR-463-3p inhibits tibial nerve regeneration via post-transcriptional suppression of SPRR1A.

Background: miRNAs have been involved in neural development, degeneration, and regeneration. MiR-463-3p is expressed in reproductive and nervous systems. In this study, the role of miR-463-3p in tibial nerve injury and regeneration was explored. Materials and methods: A model of tibial nerve injury was established with the crush method, and the levels of miR-463-3p were detected at days 0, 3, 7, 12, 18 and 24 post-injury. Then, primary tibial nerve cells were isolated from newborn mice, and miR-463-3p was respectively overexpressed and knocked down in cultured cells. Behaviors of tibial nerve cells were detected. Furthermore, bioinformatics technology was used to investigate the underlying mechanism. Results: The expression miR-463-3p was robustly increased in the injured tibial nerve in vivo and in tibial nerve cells treated with oxygen-glucose deprivation. The data on gain- and loss-of-function demonstrated that miR-463-3p negatively regulated including neurite length, percentage of cells with neurites, and cell branching in tibial nerve cells. Small proline-rich repeat protein 1 A (SPRR1A), an identified nerve regeneration associated genes, was identified as a target gene of miR-463-3p. Conclusion: Inhibition of miR-463-3p could increase SPRR1A expression in the tibial nerve tissue and improve regeneration of the tibial nerve post-injury in vivo.

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