MicroRNA-7a inhibits Isl1 expression to regulate insulin secretion by targeting Raf1 and Mapkap1 in NIT-1 cells

Both microRNA-7a (miR-7a) and LIM-homeodomain transcription factor ISL1 are important factors regulating Insulin transcription and secretion, but the functional relationship and the interacting mechanisms between miR-7a and ISL1 in pancreatic islet β-cells remain unknown. The aims of this study were thus to identify the potential interactions and signaling communication between miR-7a and ISL1 in regulating Insulin transcription and secretion in the cultured NIT-1 cells. The results show that miR-7a inhibitor upregulates Isl-1 and Insulin gene expressions, and the Insulin secretion. Whereas miR-7a mimics inhibit ISL1 and Insulin gene expressions, and decreases the Insulin secretion. Furthermore, we identified the target gene of miR-7a using dual-luciferase reporter assay, and the results demonstrate that Raf1 and Mapkap1 is a direct target gene of miR-7a, modeling RAF1/MEK/ERK1/2 and mTORC2/Akt signaling pathway to regulate Isl1 expression, and thus influencing Insulin expression and secretion. Our results indicate that therapeutic inhibition of miR-7a function could be of relevance for preserving the function of pancreatic β-cells during the course of diabetes development, implicating miR-7, ISL1, and/or the connecting molecules may act as novel targets for pharmacological or gene therapy in diabetes and related Metabolic Disease, although much detailed studies are required in the further study.