MicroRNA-19a-3p enhances the proliferation and insulin secretion, while it inhibits the apoptosis of pancreatic βcells 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 miR‑19a‑3p in diabetes. The results of RT-qPCR demonstrated that the level of miR‑19a‑3p was significantly decreased in the diabetic patients, and that the decreased miR‑50a-5p level was significantly associated with a high concentration of blood glucose. miR‑19a‑3p mimic was further used to transfect pancreatic βcells, and we found that the overexpression of miR-19a-3p promoted cell proliferation and insulin secretion, while it suppressed the apoptosis of pancreatic βcells. Suppressor of cytokine signaling3(SOCS3) was further identified as a direct target gene of miR‑19a‑3p, and its protein level was significantly decreased following the overexpression of miR‑19a‑3p. Moreover, the siRNA-induced downregulation of SOCS3 also enhanced cell proliferation and insulin secretion, while it inhibited the apoptosis of pancreatic βcells. In addition, the overexpression of SOCS3 reversed the effects of miR‑19a‑3p overexpression on cell proliferation, insulin secretion and on the apoptosis of pancreatic βcells, which further indicates that SOCS3 acts as a downstream effector in the miR-19a-3p-mediated function of pancreatic βcells. Finally, the level of SOCS3 was increased in diabetic patients, and inversely correlated with the miR‑19a‑3p level, suggesting that the downregulation of miR-19a-3p leads to the upregulation of SOCS3, which contributes to the dysfunction of pancreatic βcells. On the whole, the findings of this study suggest that miR‑19a‑3p plays an important role in βcell function, and that the miR-19a-3p/SOCS3 axis may become a potential therapeutic target for diabetes.