miR-720 Regulates Insulin Secretion by Targeting Rab35

Abstract Background: miRNAs pose a good prospect in the diagnosis and treatment of type 2 diabetes (T2D). This study aimed to investigate whether miR-720 targets Rab35 to regulate insulin secretion in MIN6 cells and its molecular mechanism, and the clinical value of miR-720 as a specific biomarker of T2D. Methods: Fifty-five samples of new diagnosis T2D patients and normal control were collected. Levels of miR-720, fasting blood glucose, insulin and other indicators of glucose and lipid metabolism were determined. We increased and decreased miR-720 expression using miR-720 mimic and inhibitor to identify the effect of miR-720 on insulin secretion in MIN6 cells, respectively. Then we used miR-720 mimic, miR-720 inhibitor and dual luciferase reporter gene assays to prove miR-720 regulate insulin secretion by targeting Rab35 in MIN6 cells. In addition, we overexpressed and silenced of Rab35 gene to detect the expression of PI3K, Akt and mTOR in MIN6 cells by RT-PCR and western blot. Results: Circulating miR-720 was significantly higher in T2D group than control group, and miR-270 was positive correlated with fasting blood glucose, while negatively correlated with insulin. Overexpression of miR-720 inhibited insulin secretion and miR-720 downregulation promoted insulin secretion. miR-720 regulated insulin secretion by targeting Rab35 in MIN6 cells. Compared with the control group, the expression of PI3K, Akt and mTOR was significantly decreased by overexpression of Rab35 gene, while silencing Rab35 gene could induce the expression of PI3K, Akt and mTOR. Conclusions: We conclude that miR-720 may as a potential biomarker for the diagnosis of T2D. Increase of miR-720 reduced Rab35 expression then activate PI3K/Akt/mTOR signal pathway, thus inhibiting insulin secretion.