Downregulation of miRNA-127-5p aggravates spinal cord injury through activating MAPK1

C Zhang1, M-M Wang, Y Zhang

  • 1Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China. sdfeydqr@163.com.

Abstract

Insights

MicroRNA-127-5p (miRNA-127-5p) downregulation worsens spinal cord injury (SCI) motor deficits. Restoring miRNA-127-5p levels improves grip strength by targeting mitogen-activated protein kinase 1 (MAPK1).

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Regenerative Medicine

Background:

  • Spinal cord injury (SCI) often leads to persistent motor dysfunction.
  • MicroRNAs (miRNAs) play crucial roles in post-injury recovery.
  • The specific role of microRNA-127-5p (miRNA-127-5p) in SCI pathophysiology remains unclear.

Purpose of the Study:

  • To investigate the role of miRNA-127-5p in motor dysfunction after SCI.
  • To determine if miRNA-127-5p regulates mitogen-activated protein kinase 1 (MAPK1) levels.
  • To elucidate the therapeutic potential of modulating miRNA-127-5p in SCI.

Main Methods:

  • An in vivo mouse model of spinal cord hitting injury was established.
  • Mice were grouped into sham, SCI, SCI + miRNA-127-5p mimics, and SCI + miRNA-127-5p mimics + MAPK1.
  • Grip strength, miRNA-127-5p and MAPK1 expression levels were assessed; molecular interactions were confirmed via bioinformatics, dual-luciferase reporter assays, and Western blot.

Main Results:

  • SCI mice exhibited significantly reduced grip strength compared to the sham group.
  • miRNA-127-5p was downregulated post-SCI, with levels decreasing over time.
  • Overexpression of miRNA-127-5p improved motor function and reduced MAPK1 protein levels; MAPK1 overexpression negated these benefits.

Conclusions:

  • Downregulation of miRNA-127-5p exacerbates motor dysfunction following spinal cord injury.
  • miRNA-127-5p exerts a protective effect by negatively regulating MAPK1.
  • Targeting miRNA-127-5p represents a potential therapeutic strategy for SCI.

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