The diagnostic value of miR-340-5p in pediatric ulcerative colitis and its molecular mechanism by targeting MAP3K2 to modulate intestinal epithelial cell dysfunction.

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作者:Meng Fanting, Han Xianlong, Ge Lingxia, Guan Nan
BACKGROUND: The incidence of pediatric ulcerative colitis (UC) is increasing yearly, and it is urgent to explore precise diagnostic biomarkers and molecular mechanisms. This study aims to investigate the diagnostic value of miR-340-5p in pediatric UC and its molecular mechanism mediated through targeting MAP3K2. METHODS: Eighty-five pediatric UC patients and 50 healthy controls were enrolled. The expression levels of miR-340-5p and MAP3K2 were detected by qRT-PCR, and Pearson's correlation analysis was conducted. An in vitro model was established by inducing HT-29 cells with dextran sulfate sodium. The target was verified by dual-luciferase assay. Flow cytometry, ELISA, and oxidative stress detection were used to verify the cellular functions regulated by the miR-340-5p/MAP3K2 axis. RESULTS: In pediatric patients with UC, miR-340-5p was significantly downregulated and negatively correlated with PUCAI, CRP, and ESR (P < 0.0001). Additionally, the diagnostic area of miR-340-5p under the ROC curve was 0.908. Mechanistically, miR-340-5p directly interacts with MAP3K2, leading to suppressed expression of its mRNA and protein. Functional experiments revealed that miR-340-5p overexpression reversed DSS-induced exacerbated cell apoptosis, reduced levels of TNF-α, IL-6, IL-17, IL-1β, and MDA, and increased GSH. Conversely, the beneficial effects of miR-340-5p were attenuated by oe-MAP3K2 overexpression. CONCLUSIONS: miR-340-5p may serve as a diagnostic biomarker for pediatric UC and exerts its effects by targeting MAP3K2 to regulate cell apoptosis, inflammatory responses, and oxidative stress.

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