MicroRNA-19a-3p enhances the proliferation and insulin secretion, while it inhibits the apoptosis of pancreatic cells via the inhibition of SOCS3

Abstract

MicroRNAs (miRNAs or miRs), a group of small non coding RNAs, have been demonstrated to play key roles in various physicological processes and diseases, including diabetes, the most common metabolic disorder. However, the underlying mechanisms remains largely unknown. In this study, we aimed to investigate the role of miR19a3p in diabetes. The results of RT-qPCR demonstrated that the level of miR19a3p was significantly decreased in the diabetic patients, and that the decreased miR50a-5p level was significantly associated with a high concentration of blood glucose. miR19a3p mimic was further used to transfect pancreatic cells, and we found that the overexpression of miR19a3p promoted cell proliferation and insulin secretion, while it suppressed the apoptosis of pancreatic cells. Suppressor of cytokine signaling 3 (SOCS3) was further identified as a direct target gene of miR19a3p, and its protein level was significantly decreased following the overexpression of miR19a3p. Moreover, the siRNA-induced downregulation of SOCS3 also enhanced cell proliferation and insulin secretion, while it inhibited the apoptosis of pancreatic cells. In addition, the overexpression of SOCS3 reversed the effects of miR19a3p overexpression on cell proliferation, insulin secretion and on the apoptosis of pancreatic cells, which further indicates that SOCS3 acts as a downstream effector in the miR9a3p-mediated function of pancreatic cells. Finally, the level of SOCS3 was increased in diabetic patients, and inversely correlated with the miR19a3p level, suggesting that the downregulation of miR19a3p leads to the upregulation of SOCS3, which contributes to the dysfunction of pancreatic cells. On the whole, the findings of this study suggest that miR9a3p plays an important role in cell function, and that the miR19a3p/SOCS3 axis may become a potential therapeutic target for diabetes.