LncRNA MEG3 regulates autophagy and pyroptosis via FOXO1 in pancreatic β-cells

Abstract

Diabetes mellitus (DM) is a chronic metabolic disease, and its exact pathogenesis remains unclear. Autophagy and pyroptosis play an important role in pancreatic β-cells inflammation and death. Recent advances revealed that LncRNA MEG3 (MEG3) promotes insulin secretion and inhibits pancreatic β-cells apoptosis in DM. However, its effect on pancreatic β-cells autophagy and pyroptosis remains elusive. This study investigated whether MEG3 can regulate autophagy and pyroptosis through FOXO1 in pancreatic β-cells. Here, a significant reduction of MEG3 and FOXO1 expression was found in the DM group of mouse model, in company with, autophagy dysfunction and pyroptosis hyperactivity. In the cell model, the level of autophagy was increased in high-glucose (HG) induced INS-1 cells. Besides, we found that MEG3 or FOXO1 knockdown leads to decreased autophagy, and up-regulated pyroptosis in HG-induced INS-1 cells. Furthermore, the deficiency of MEG3 significantly decreased FOXO1 expression. In addition, the specific inhibitors of autophagy also increased pyroptosis-related protein expression. These results demonstrate that MEG3 may adjust both autophagy and pyroptosis through FOXO1 in pancreatic β-cells. Moreover, we also first verified that inhibiting autophagy can promote pyroptosis in HG-induced INS-1 cells.