MiR-877-5p targets PDK-1 to promote aspirin-induced apoptosis in gastric mucosal cells

Lu Yuyu1, Zhang Shikun2, Zhang Zhenyu3

  • 1Department of ICU, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China.

Die Pharmazie
|June 3, 2021
PubMed

Insights

This study reveals that miR-877-5p plays a key role in aspirin-induced gastric mucosal injury. Upregulation of miR-877-5p promotes cell apoptosis by targeting PDK1, suggesting it as a potential therapeutic target.

Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Biochemistry

Background:

  • Aspirin is a common nonsteroidal anti-inflammatory drug.
  • Aspirin use can lead to significant gastric mucosal injury.
  • The molecular mechanisms underlying aspirin-induced gastric injury require further elucidation.

Purpose of the Study:

  • To investigate the role of microRNA (miR)-877-5p in aspirin-induced gastric mucosal injury.
  • To identify the molecular targets and pathways regulated by miR-877-5p in this context.

Main Methods:

  • MiRNA microarray analysis of human gastric mucosal samples.
  • In vitro studies using gastric epithelial cells (GES-1) treated with aspirin.
  • Transfection with miR-877-5p mimics/inhibitors.
  • Quantitative real-time PCR (qRT-PCR), flow cytometry, and Western blot assays.
  • Luciferase reporter assay to validate target gene interaction.

Main Results:

  • MiR-877-5p expression was significantly higher in gastric mucosal injury samples compared to normal samples.
  • Depletion of miR-877-5p reduced aspirin-induced apoptosis in GES-1 cells.
  • PDK1 was identified as a direct target gene of miR-877-5p.
  • PDK1 inhibited aspirin-induced apoptosis, an effect reversed by PDK1 knockdown.

Conclusions:

  • MiR-877-5p plays a protective role against aspirin-induced gastric mucosal injury.
  • MiR-877-5p exerts its effect by targeting and downregulating PDK1, thereby modulating apoptosis.
  • MiR-877-5p represents a potential therapeutic target for managing aspirin-induced gastric damage.

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