miR-765 targeting PDX1 impairs pancreatic β-cell function to induce type 2 diabetes

Type 2 diabetes (T2DM) is a chronic metabolism disorder with a symptom as pancreatic β-cell dysfunction. In this study, the bioinformatics analysis identified the key regulators (PDX1 and miR-765) in T2DM. By qRT-PCR and western blotting, miR-765 with high expression and PDX1 with low expression were observed in blood samples from T2DM patients and the T2DM cell model. Together with GSIS assay, CCK-8, TUNEL assay, glycolysis assay, and mitochondrial respiration assay, miR-765 overexpression impaired insulin secretion cell viability, glycolysis, and mitochondrial respiration, while enhanced cell apoptosis in pancreatic β-cell. The Luciferase reporter, RIP, and RNA pull-down assays showed that PDX1 was the target gene of miR-765 in pancreatic β-cell. Besides, the negative effect of miR-765 on pancreatic β-cell could be overturned by PDX1 overexpression. In conclusion, we confirmed that miR-765 could cause a detrimental effect on pancreatic β-cell survival and function by targeting PDX1, which might provide new insight for T2DM therapy.