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.