LncRNA OIP5-AS1 regulates ferroptosis and mitochondrial dysfunction-mediated apoptosis in spinal cord injury by

Zhensong Jiang1, Weimin Zhang1, Jianru Zhang2

  • 1Department of Spine Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.

Heliyon
|September 23, 2024
PubMed
Abstract

Insights

Overexpression of LncRNA OIP5-AS1 inhibits ferroptosis and apoptosis, improving spinal cord injury recovery by regulating the miR-128-3p/Nrf2 pathway. This offers a potential therapeutic strategy for neurological damage.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Death Research

Background:

  • Ferroptosis is a key neuronal death pathway in spinal cord injury (SCI) and inflammation.
  • MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are critical regulators of ferroptosis.
  • LncRNA OIP5-AS1's role in ferroptosis and mitochondrial dysfunction post-SCI requires investigation.

Purpose of the Study:

  • To investigate the inhibitory effect of LncRNA OIP5-AS1 on ferroptosis.
  • To explore the role of LncRNA OIP5-AS1 in mitochondrial dysfunction-mediated apoptosis in SCI.
  • To elucidate the regulatory mechanism involving LncRNA OIP5-AS1, miR-128-3p, and Nrf2 in SCI.

Main Methods:

  • Established ferric ammonium citrate (FAC)-induced cell and SCI rat models.
  • Analyzed LncRNA OIP5-AS1, miR-128-3p, and Nrf2 expression and interactions.
  • Assessed cell viability, apoptosis, ferroptosis, and mitochondrial dysfunction markers in vitro and in vivo.
  • Utilized histopathologic slide staining for SCI evaluation.

Main Results:

  • LncRNA OIP5-AS1 was downregulated in SCI models.
  • LncRNA OIP5-AS1 deficiency exacerbated SCI by reducing Nrf2 via miR-128-3p, increasing apoptosis, ferroptosis, and mitochondrial dysfunction.
  • Overexpression of LncRNA OIP5-AS1 ameliorated SCI by inhibiting these detrimental processes.

Conclusions:

  • LncRNA OIP5-AS1 overexpression enhances SCI recovery.
  • This effect is mediated by regulating the miR-128-3p/Nrf2 axis.
  • LncRNA OIP5-AS1 represents a potential therapeutic target for SCI treatment.

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