Abnormal Expression of microRNA-296-3p in Type 2 Diabetes Patients and its Role in Pancreatic β-Cells Function by Targeting Tensin Homolog Deleted on Chromosome Ten.

Diabetes mellitus (DM), a familiar disease, is characterized by high blood glucose levels owing to insulin deficiency. Researches have suggested that the incidence rate of diabetes is increasing and it has become an important global epidemic. The type 2 diabetes mellitus (T2DM) is featured with pancreatic β-cell loss and lack of insulin release. Nevertheless, the therapeutic methods that was helpful to improve pancreatic β-cell damage still unclear. Previous report have revealed that tensin homolog deleted on chromosome ten (PTEN) was remarkably enhanced in serum of patients with T2DM, and the lack of PTEN may prevent function deficiency of pancreatic β-cells in DM. However, the underlying mechanisms are rarely illustrated. Our purpose in this report was to illustrated the roles and potential mechanism of microRNA-296-3p (miR-296-3p) in uric acid (UA)-induced pancreatic β-cell injury. The direct target of miR-296-3p was predicted and verified by dual-luciferase reporter system and TargetScan assay. Moreover, Min6 cells were induced by 5 mg/dl UA and the cell proliferation, apoptosis, and insulin release were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and glucose-stimulated insulin secretion (GSIS), respectively. Quantitative reverse transcription PCR (qRT-PCR) and western blot assay were adopted to analyze the levels of miR-296-3p, PTEN and apoptosis-related proteins. TargetScan and Dual-luciferase reporter system confirmed that PTEN directly target miR-296-3p. MiR-296-3p was downregulated in UA-induced Min6 cells and the serum of type 2 diabetes patients, while PTEN was upregulated in UA-induced Min6 cells. Upregulation of miR-296-3p by mimic dramatically promoted miR-296-3p level and decreased PTEN level. Besides, PTEN was over-expressed after PTEN-plasmid transfection. UA treatment prominently decreased cell viability, promoted apoptotic cells, enhanced Bax levels, declined Bcl-2 level as well as decreased insulin release in Min6 cells. MiR-296-3p mimic significantly alleviated UA-induced pancreatic β-cells dysfunction, and PTEN-plasmid eliminated the protective effect of miR-296-3p on insulin release, cell viability, and apoptosis of pancreatic β-cells in UA-stimulated Min6 cells. In summary, our findings revealed that upregulation of miR-296-3p protected pancreatic β-cells functions against UA-induced dysfunction by targeting PTEN, which provides a novel agent for type 2 diabetes treatment.