Abnormal expression of miR-454-3p in type 2 diabetes mellitus induces dysfunction of pancreatic β cells by regulating Yy1.

Abstract

ObjectiveImpairment of pancreatic β cells is a pathophysiological feature of type 2 diabetes mellitus (T2DM). However, whether abnormally dysregulated miR-454-3p in T2DM is related to the dysfunction of pancreatic β cell remains to be further investigated.MethodsFirst, T2DM patients and healthy subjects were recruited to measure miR-454-3p. Subsequently, pancreatic β cells were cultured with high glucose. The role of miR-454-3p in insulin synthesis, secretion, cell proliferation, and apoptosis were investigated by RT-qPCR, Glucose-stimulated insulin secretion determination, cell counting kit-8, and flow cytometry assays. The target mRNA of miR-454-3p was predicted using bioinformatics software. Then, the targeted binding relationships between the above two factors were verified through RNA Immunoprecipitation and Dual-Luciferase Reporter assays.ResultsThe expression of miR-454-3p was increased in T2DM patients and pancreatic β cells cultured with high glucose. Moreover, miR-454-3p was positively correlated with FPG and HbA1c levels in patients. In cell experiments, miR-454-3p inhibitors significantly improved the function of pancreatic β cells, including increased insulin synthesis and secretion, and promoted proliferation. Moreover, silencing Yy1 reversed the protective effect of miR-454-3p inhibitors on pancreatic β cells.ConclusionmiR-454-3p, which is dysregulated in T2DM, promotes the damage of pancreatic β cells by regulating Yy1, thus aggravating T2DM.