Recently, microRNAs (miRNAs) have been suggested to play important roles in the pathophysiology of type 2 diabetes mellitus (T2DM). In this study, we explored the role of miR-486-5p in T2DM. MiR-486-5p was significantly downregulated in the serum of T2DM patients when compared to that of healthy volunteers, and miR-486-5p expression level was negative correlated with blood glucose levels of T2DM patients. Overexpression of miR-486-5p promoted cell proliferation, enhanced insulin secretion and inhibited cell apoptosis of pancreatic β-cell line (INS-1 cells). On the other hand, knockdown of miR-486-5p had the opposite effects in INS-1 cells. The bio-informatics analysis by using TargetScan revealed phosphatase and tensin homolog (PTEN) and Forkhead Box O1 (FOXO1) were downstream targets of miR-486-5p, and the interaction between miR-486-5p and PTEN (or FOXO1) was validated by luciferase reporter assay. In addition, miR-486-5p negatively regulated the mRNA and protein expression of PTEN and FOXO1. Overexpression of PTEN (or FOXO1) suppressed insulin secretion in glucose stimulation, inhibited cell proliferation, and induced cell apoptosis, and partially abolished the effects of miR-486-5p overexpression on insulin secretion, cell proliferation and cell apoptosis of INS-1 cells. In conclusion, our results revealed that miR-486-5p promoted pancreatic cell proliferation, increased insulin sensitivity and inhibited apoptosis by targeting PTEN and FOXO1.
Tian et al. (Wed,) studied this question.