miR-378-3p alleviates contusion spinal cord injury by negatively regulating ATG12

Haocong Zhang1, Hailong Yu1, Huifeng Yang1

  • 1Department of Orthopaedics, General Hospital of Northern Theater Command, Shenyang, China.

Insights

MicroRNA-378-3p (miR-378-3p) protects nerve cells from apoptosis and improves motor function after spinal cord injury (SCI). Upregulating miR-378-3p in SCI models reduces nerve cell death and enhances neurological recovery.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) are critical regulators in spinal cord injury (SCI) pathogenesis.
  • The specific roles of miR-378-3p and autophagy-related 12 (ATG12) in SCI remain incompletely understood.

Purpose of the Study:

  • To investigate the functional relationship between miR-378-3p and ATG12 in SCI.
  • To evaluate the therapeutic potential of miR-378-3p in a rat model of contusion SCI.

Main Methods:

  • Quantitative real-time PCR (RT-qPCR) for gene expression analysis.
  • Cell viability (CCK-8) and membrane integrity (LDH) assays.
  • Dual-luciferase reporter assay to confirm direct interaction.
  • Basso, Beattie and Bresnahan (BBB) score and motor deficit index for functional assessment in rats.

Main Results:

  • miR-378-3p was downregulated, while ATG12 was upregulated in SCI tissues and hypoxic cells.
  • Hypoxia-induced factor 1-α (HIF-1α) repressed miR-378-3p expression.
  • Overexpression of miR-378-3p inhibited apoptosis by directly repressing ATG12.
  • miR-378-3p administration improved hindlimb motor function and neurological recovery in rats with contusion SCI.

Conclusions:

  • miR-378-3p acts as a neuroprotective agent by suppressing nerve cell apoptosis through ATG12 repression.
  • Restoring miR-378-3p levels offers a promising therapeutic strategy for ameliorating functional deficits following spinal cord injury.