MiR-34a regulates Schwann cell proliferation and migration by targeting CNTN2.

Abstract

The proliferation and migration of Schwann cells contribute to axonal outgrowth and functional recovery after peripheral nerve injury. Previously, several microRNAs were abnormally expressed after peripheral nerve injury and they played important roles in peripheral nerve regeneration. However, the role and underlying mechanism of miR-34a in peripheral nerve injury remain largely unknown. The levels of miR-34a and contactin-2 (CNTN2) were detected by quantitative real-time PCR. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and transwell assays were used to examine cell proliferation and migration, respectively. The protein level of CNTN2 was measured by western blot. The binding sites of miR-34a and CNTN2 were predicted by the online software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Following sciatic nerve injury, the expression of miR-34a was downregulated in the crushed nerve segment, reaching a minimum at the seventh day. Knockdown of miR-34a enhanced the axon outgrowth of dorsal root ganglion neurons. Moreover, miR-34a overexpression evidently inhibited the proliferation of Schwann cells, whereas its knockdown showed the opposite effects. In addition, CNTN2 was a direct target of miR-34a and its expression was negatively regulated by miR-34a in the crushed nerve segment. Besides, CNTN2 overexpression or knockdown could reverse the effects of miR-34a upregulation or downregulation on proliferation and migration of Schwann cells, respectively. Collectively, miR-34a inhibited the proliferation and migration of Schwann cells via targeting CNTN2, which might provide a new approach to peripheral nerve regeneration.