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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.
Abstract:
This study aimed to investigate the role of miR-877-5p in aspirin-induced gastric mucosal injury. MiRNA microarray analysis was performed using paired gastric mucosal samples to find differentially expressed miRNAs. miR-877-5p was selected for subsequent analyses. Used as a model system, gastric epithelial cells (GES-1) were transfected with miR-877-5p mimic/inhibitor, then treated with aspirin. The expression of miR-877-5p in GES-1 cells was examined using quantitative real-time PCR (qRT-PCR). Flow cytometry analysis was used to detect cell apoptosis. Western blot assay was used to measure the protein levels of PDK1. The interaction between miR-877-5p and PDK1 was determined by luciferase reporter assay. The expression of miR-877-5p in gastric mucosal injury samples was higher than that in normal samples. Also, depletion of miR-877-5p reduced the apoptosis of GES-1 cells. Luciferase reporting assay confirmed that PDK1 was a target gene of miR-877-5p. PDK1 inhibited the apoptosis of GES-1 cells treated by aspirin. Moreover, this inhibitory effect was abrogated after PDK1 knockdown. Downregulation of miR-877-5p reduced the apoptosis by targeting PDK1 in GES-1 cells treated by aspirin, indicating that miR-877-5p may be a potential therapeutic target for gastric mucosal injury caused by aspirin.
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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