Long non-coding RNA MALAT1 promotes the proliferation and migration of Schwann cells by elevating BDNF through sponging miR-129-5p

Exp Cell Res. 2020 May 1;390(1):111937. doi: 10.1016/j.yexcr.2020.111937. Epub 2020 Mar 2.

Abstract

The proliferation and migration of Schwann cells contribute to nerve regeneration after peripheral nerve injury (PNI). In recent years, roles of long non-coding RNAs (lncRNAs) in PNI have been gradually uncovered. However, a highly conserved nuclear lncRNA Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in peripheral nerve regeneration remains enigmatic. MALAT1 expression in injured sciatic nerve of mice with PNI was measured by real-time PCR. The proliferative and migrative abilities of Schwann cells were determined after upregulating or downregulating Malat1. The relationship among MALAT1, miR-129-5p, and BDNF was measured. In this study, we found elevated MALAT1 expression in injured sciatic nerve. MALAT1 upregulation in Schwann cells promoted cell proliferation and migration. However, downregulation of MALAT1 caused the suppression of Schwann cell proliferation and migration. Mechanistically, we discovered MALAT1 negatively regulated miR-129-5p through directly binding. Brain-derived neurotrophic factor (BDNF) was a target of miR-129-5p. MALAT1 positively modulated BDNF expression and secretion via decreasing miR-129-5p. Downregulation of BDNF rescued the influences of MALAT1 overexpression on Schwann cell proliferation and migration. In conclusion, MALAT1 was enhanced after PNI and it promoted the proliferation and migration of Schwann cells through sponging miR-129-5p to increase BDNF expression and secretion. This study proved that MALAT1 may be a vital regulator in peripheral nerve regeneration.

Keywords: Long non-coding RNA MALAT1; Migration; Peripheral nerve injury; Proliferation; Schwann cells.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Movement*
  • Cell Proliferation*
  • Cells, Cultured
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Schwann Cells / metabolism*
  • Schwann Cells / physiology

Substances

  • Brain-Derived Neurotrophic Factor
  • MIRN129 microRNA, mouse
  • Malat1 long non-coding RNA, mouse
  • MicroRNAs
  • RNA, Long Noncoding