The Effect And Mechanism Of MiR-200c Regulating Pyroptosis By NEK7 In Ulcerative Colitis

Objective: The etiology and pathogenesis of ulcerative colitis,a type of inflammatory bowel disease,are still not fully understood.Mi R-200c is an important regulator of programmed cell death.By the weighted correlation network analysis of network ship called GSE75214,the research group found that miR-200c had a negative correlation with NLRP3(R =-0.629,p < 0.01).Based on our previous research,NEK7 interacted with NLRP3 to modulate NLRP3 inflammasome activation,therefore modulating pyroptosis in MODE-K cells and DSS-induced chronic colitis in mice.The research group speculated it that miR-200c might regulate the pyrotosis by NEK7 and explored the effect and mechanism of miR-200c/NEK7 axis in ulcerative colitis.Methods: The differential expression of miR-200c and NEK7 in ulcerative colitis tissues and normal colon tissues was compared.When miR-200c was in the low or heigh expression,the differential expression of inflammatory factors and pyroptosis associated proteins in the MODE-K cells and the differential degree of inflammation in the animal model of Colitis were observed.Then,the dual-luciferase experiment was used to prove it that whether miR-200c could target NEK7.Results: In clinical specimens,miR-200c expression was low in ulcerative colitis lesions but high in normal colon tissues,whereas NEK7 was the reverse.There might be a negative correlation between miR-200c and NEK7.In MODE-K cells,miR-200c’ might bind with NEK7,inhibit the expression of inflammatory factors and pyroptosis associated proteins,modulate pyroptosis and regulate the development of ulcerative colitis.In mouse colitis model,miR-200c could prevent the colon length from shortening,inhibit the weight loss,restrain the increase of DAI score,reduce the inflammatory degree of colitis and relieve the symptoms of colitis.Conclusion: MIR-200c might target NEK7 to prevent the expression of inflammatory factors and pyroptosis related proteins,inhibit the cell pyroptosis,relieve the symptoms of ulcerative colitis,and regulate the development of ulcerative colitis.