MicroRNA‑138‑5p regulates the development of spinal cord injury by targeting SIRT1

Jinchuan Chen1, Rujie Qin1

  • 1Department of Spine Surgery, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu 222000, P.R. China.

Insights

MicroRNA-138-5p is upregulated in spinal cord injury (SCI), promoting inflammation and cell death. Inhibiting this microRNA (miRNA) and targeting SIRT1 may offer new therapeutic strategies for SCI treatment.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • MicroRNAs (miRs) are critical regulators in the pathogenesis of spinal cord injury (SCI).
  • The specific role and regulatory mechanisms of miR-138-5p in SCI remain incompletely understood.

Purpose of the Study:

  • To investigate the role of miR-138-5p in the development and progression of spinal cord injury (SCI).
  • To elucidate the anti-inflammatory effects and underlying molecular mechanisms of miR-138-5p in SCI.

Main Methods:

  • Expression analysis of miR-138-5p and sirtuin 1 (SIRT1) using RT-qPCR and Western blotting in SCI models (in vivo, in vitro, and human patients).
  • Bioinformatics and dual-luciferase reporter assays to confirm the interaction between miR-138-5p and SIRT1.
  • Cellular assays (MTT, flow cytometry, ELISA) to assess cell viability, apoptosis, and inflammatory cytokine levels (TNF-α, IL-1β, IL-6) following transfection and treatment.

Main Results:

  • miR-138-5p was significantly upregulated, while SIRT1 was downregulated in SCI models.
  • Downregulation of miR-138-5p enhanced cell viability, reduced apoptosis, and attenuated pro-inflammatory responses in PC12 cells.
  • These protective effects were reversed by SIRT1 knockdown, indicating SIRT1 mediates miR-138-5p's function via the PTEN/AKT pathway.

Conclusions:

  • miR-138-5p exacerbates SCI by promoting inflammation and apoptosis, partly through modulating the PTEN/AKT pathway via SIRT1.
  • Targeting miR-138-5p and its downstream effectors like SIRT1 presents a potential therapeutic avenue for managing spinal cord injury.