Abstract
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the lower gastrointestinal tract with unknown etiology. In our previous study, NOD-like receptor 3 (NLRP3) inflammasome activation requiring the interaction of NLRP3 with NIMA Related Kinase 7 (NEK7) had been reported to regulate MODE-K cell pyroptosis and dextran sulfate sodium (DSS)-induced murine colitis. In the present study, miR-200c was closely related to IBD using weighted gene correlation network analysis (WGCNA). MicroRNA-200c (miR-200c) expression was down-regulated in IBD samples and negatively correlated with NLRP3. In MODE-K cells, miR-200c overexpression inhibited cellular inflammation; under adenosine triphosphate (ATP) and lipopolysaccharides (LPS) co-stimulation, miR-200c overexpression attenuated ATP and LPS-induced cell pyroptosis. In the DSS-induced IBD mice model, miR-200c overexpression alleviated DSS-induced IBD symptoms and improved physiological and biochemical indexes. Through direct targeting, miR-200c inhibited NEK7 expression. In MODE-K cells, NEK7 overexpression promoted cellular inflammation and ATP and LPS-induced cell pyroptosis; when co-transduced into MODE-K cells, NEK7 overexpression partially attenuated miR-200c agomir effects on cellular inflammation and ATP and LPS-induced cell pyroptosis. In conclusion, miR-200c, through targeting NEK7, could decrease cellular inflammation levels and NLRP3 inflammasome-related MODE-K cell pyroptosis in vitro and improve DSS-induced murine IBD symptoms in vivo.