RETRACTED: NF-B Inhibits the Occurrence of Type 1 Diabetes Through Microrna-150-dependent PUMA Degradation (retracted Article. See Vol. 324, 2023)

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