Loc680254 regulates Schwann cell proliferation through Psrc1 and Ska1 as a microRNA sponge following sciatic nerve injury

Glia. 2021 Oct;69(10):2391-2403. doi: 10.1002/glia.24045. Epub 2021 Jun 11.

Abstract

Peripheral nerve injury triggers sequential phenotype alterations in Schwann cells, which are critical for axonal regeneration. Long noncoding RNAs (lncRNAs) are long transcripts without obvious coding potential. It has been reported that lncRNAs participate in diverse biological processes and diseases. However, the role of lncRNA in Schwann cells and peripheral nerve regeneration is unclear. Here, we identified an lncRNA, loc680254, which is upregulated in rat sciatic nerve after peripheral nerve injury. The loc680254 knockdown inhibits Schwann cell proliferation, enhances apoptosis, and hinders cell cycle, while loc680254 overexpression has the opposite effect. Mechanically, we found that loc680254 might act as a microRNA sponge to regulate the expression of mitosis-related gene, spindle and kinetochore associated complex subunit 1 (Ska1) and proline/serine-rich coiled-coil 1 (Psrc1). Silencing of Psrc1 or Ska1 attenuates the effect of loc680254 overexpression on Schwann cell proliferation. Finally, we repaired the rat sciatic nerve gap with chitosan scaffolds loaded with loc680254-overexpressing Schwann cells and evaluated axon regeneration and functional recovery. Our results indicated that loc680254 is a new potential modulator for Schwann cell proliferation, which could be targeted to develop novel therapeutic strategies for peripheral nerve repair.

Keywords: Schwann cells; cell proliferation; competing endogenous RNA; lncRNA; peripheral nerve injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Cell Proliferation / genetics
  • Chromosomal Proteins, Non-Histone*
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Nerve Regeneration / physiology
  • Peripheral Nerve Injuries* / metabolism
  • Phosphoproteins*
  • RNA, Long Noncoding*
  • Rats
  • Rats, Sprague-Dawley
  • Schwann Cells / metabolism
  • Sciatic Nerve* / injuries
  • Sciatic Nerve* / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • MicroRNAs
  • Phosphoproteins
  • RNA, Long Noncoding