MiR-9 inhibits Schwann cell migration by targeting Cthrc1 following sciatic nerve injury

J Cell Sci. 2014 Mar 1;127(Pt 5):967-76. doi: 10.1242/jcs.131672. Epub 2014 Jan 10.


The regulative effects of microRNAs (miRNAs) on responses of Schwann cells to a nerve injury stimulus are not yet clear. In this study, we noted that the expression of eight miRNAs was downregulated at different time points following rat sciatic nerve transection, and found that 368 potential targets of these eight miRNAs were mainly involved in phenotypic modulation of Schwann cells. Of these miRNAs, miR-9 was identified as an important functional regulator of Schwann cell migration that was a crucial regenerative response of Schwann cells to nerve injury. In vitro, upregulated expression of miR-9 inhibited Schwann cell migration, whereas silencing of miR-9 promoted Schwann cell migration. Intriguingly, miR-9 exerted this regulative function by directly targeting collagen triple helix repeat containing protein 1 (CTHRC1), which in turn inactivated downstream Rac1 GTPase. Rac1 inhibitor reduced the promotive effects of anti-miR-9 on Schwann cell migration. In vivo, high expression of miR-9 reduced Schwann cell migration within a regenerative nerve microenvironment. Collectively, our results confirmed the role of miR-9 in regulating Schwann cell migration after nerve injury, thus offering a new approach to peripheral nerve repair.

Keywords: CTHRC1; Migration; Peripheral nerve regeneration; Schwann cell; miR-9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Movement
  • Cells, Cultured
  • Down-Regulation
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Male
  • MicroRNAs / physiology*
  • Nerve Regeneration*
  • Peripheral Nerve Injuries / genetics
  • Peripheral Nerve Injuries / metabolism*
  • RNA Interference
  • Rats
  • Rats, Sprague-Dawley
  • Schwann Cells / physiology*
  • Sciatic Nerve / injuries
  • Sciatic Nerve / physiology*
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism


  • 3' Untranslated Regions
  • Cthrc1 protein, rat
  • Glycoproteins
  • MIRN9 microRNA, rat
  • MicroRNAs
  • Rac1 protein, rat
  • rac1 GTP-Binding Protein