RETRACTED: NF-κB inhibits the occurrence of type 1 diabetes through microRNA-150-dependent PUMA degradation

Abstract

Type 1 diabetes (T1D) is the most common autoimmune disease that affects a global scale. Accumulating evidence has indicated, nuclear factor kappa B (NF-κB) and some microRNAs (miRNAs) as important biomarkers participating in the development of T1D. Thus, we aimed to determine the role of NF-κB and miR-150 in the development of T1D and to unravel the molecular mechanism. Non-obese diabetic mice were used for the T1D model establishment by injecting with streptozotocin. Besides, pancreatic islet β cells, separated from T1D mice, were induced by interferon-γ and tumor necrosis factor-α for 3days to mimic T1D damage. The expression of NF-κB p65, miR-150, and p53 up-regulated modulator of apoptosis (PUMA) was evaluated by RT-qPCR, while the expression of PUMA, p65, and apoptotic proteins in pancreatic islet β cells were determined by western blot analysis. Besides, inflammatory factors IL-17A, IL-2, IFN-γ, and IL-4 were detected by ELISA. The relationship among NF-κB, miR-150, and PUMA was analyzed by the dual-luciferase reporter gene, chromatin- and RNA-immunoprecipitation assays, respectively. Restoration of NF-κB reduced the incidence of T1D in mice. Over-expressed NF-κB inhibited the release of inflammatory factors and apoptosis in pancreatic islet β cells. PUMA was confirmed to be a potential target gene of miR-150. miR-150 suppressed PUMA to inhibit the T1D-induced inflammation and β cell apoptosis whereas NF-κB activated the miR-150 expression by binding to the miR-150 promoter, thereby preventing the T1D-induced inflammation and β cell apoptosis. NF-κB/miR-150/PUMA may serve as potential therapeutic targets for T1D.