miR-320a induces pancreatic 13 cells dysfunction in diabetes by inhibiting MafF

A variety of studies indicate that microRNAs (miRNAs) are involved in diabetes. However, the direct role of miR-320a in the pathophysiology of pancreatic beta cells under diabetes mellitus remains unclear. In the current study, islet transplantation and hyperglycemic clamp assays were performed in miR-320a transgenic mice to explore the effects of miR320a on pancreatic beta cells in vivo. Meanwhile, beta cell-specific overexpression or inhibition of miR-320a was delivered by adeno-associated virus (AAV8). In vitro, overexpression or downregulation of miR-320a was introduced in cultured rat islet tumor cells (INS1). RNA immunoprecipitation sequencing (RIP-Seq), luciferase reporter assay, and western blotting were performed to identify the target genes. Results showed that miR-320a was increased in the pancreatic beta cells from high-fat-diet (HFD)-treated mice. Overexpression of miR-320a could not only deteriorate the HFD-induced pancreatic islet dysfunction, but also initiate pancreatic islet dysfunction spontaneously in vivo. Meanwhile, miR-320a increased the ROS level, inhibited proliferation, and induced apoptosis of cultured beta cells in vitro. Finally, we identified that MafF was the target of miR-320a that responsible for the dysfunction of pancreatic beta cells. Our data suggested that miR-320a could damage the pancreatic beta cells directly and might be a potential therapeutic target of diabetes.

Automated summary

Studies have shown that miR-320a is increased in pancreatic beta cells in diabetes and can lead to dysfunction by promoting ROS levels, inhibiting proliferation, and inducing apoptosis. The target gene of miR-320a, MafF, plays a role in the dysfunction of pancreatic beta cells. These findings suggest that miR-320a may be a potential therapeutic target for diabetes.