The mechanism of miR-363-3p/DUSP10 signaling pathway involved in the gastric mucosal injury induced by clopidogrel

Abstract

Clopidogrel-induced gastric injury is an important clinical problem. However, the exact mechanism is still unclarified. Increasing evidence indicates that miRNAs may be involved in the pathogenesis of gastric mucosal injury. In this study, the aim was to investigate the role of miR-363-3p in the gastric mucosal injury caused by clopidogrel. MiRNA microarray analysis was performed using paired gastric mucosal in order to find differential expression of miRNAs. The levels of miR-363-3p were examined in gastric mucosal injury caused by clopidogrel. The GES-1 cells were used as a model system, miR-363-3p mimic/inhibitor was transfected into GES-1 cells, then GES-1 cells were treated with clopidogrel. The levels of miR-363-3p and DUSP10 were examined in GES-1 cells using quantitative real-time PCR (qRT-PCR). CCK-8 assay and flow cytometry analysis were used to detect cell proliferation and apoptosis, respectively. Western blot assay was used to measure the protein levels of DUSP10. The interaction between miR-363-3p and DUSP10 was determined by luciferase reporter assay. MiR-363-3p was selected as a differentially expressed miRNA. The expression of miR-363-3p in gastric mucosal injury caused by clopidogrel was higher than that in normal samples. Also, depletion of miR-363-3p increased the proliferation of GES-1 cells and reduced the apoptosis. Luciferase-reporting assay results confirmed that DUSP10 was one of the target genes of miR-363-3p. DUSP10 inhibited apoptosis in GES-1 cells treated by clopidogrel. Moreover, DUSP10 knockdown abrogated the inhibitory effects on apoptosis in GES-1 cells mediated by miR-363-3p inhibitor. Knockdown of miR-363-3p increased the proliferation and reduced the apoptosis by targeting DUSP10 in GES-1 cells treated by clopidogrel, indicating that miR-363-3p may be a potential therapeutic target for gastric mucosal injury caused by clopidogrel.