Silencing circRNA LRP6 down-regulates PRMT1 to improve the streptozocin-induced pancreatic β-cell injury and insulin secretion by sponging miR-9-5p.

Due to the sedentary lifestyles of people, the number of obese people is increasing alarmingly, which leads to the high prevalence of diabetes mellitus (DM). It was reported that circularRNA (circRNA) LRP6 was upregulated in HG-treated mesangial cells, and it could regulate high glucose-induced cell injury via sponging miR-205. Thus, the aim of this study was to explore the underlying pathogenesis of DM. Streptozocin (STZ) was used to stimulate the in vitro model of pancreatic β-cell injury. Then, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and methyl thiazolyl tetrazolium (MTT) assay were used to evaluate the expression of circLRP6 and the cell viability in STZ-challenged INS-1 cells, respectively. After knocking down circLRP6, the cell viability and apoptosis were respectively measured by MTT and TdT-mediated dUTP nick-end labeling (TUNEL) staining, and insulin release and oxidative stress were respectively measured by enzyme-linked immunosorbent assay (ELISA) and corresponding kits. After the interactions among circLRP6, PRMT1, and miR-9-5p were predicted and confirmed, the above mentioned assays were conducted again. The expression of circLRP6 was elevated while cell viability was decreased after INS-1 cells were exposed to STZ. Silencing circLRP6 resulted in an increase in the cell viability, a decrease in the cell apoptosis, together with more insulin release. The circLRP6/miR-9-5p/PRMT1 regulatory network was then confirmed, which affected the cell viability, apoptosis, insulin release, and oxidative stress in STZ-challenged INS-1 cells. In conclusion, this study first provides evidence that the circLRP6/miR-9-5p/PRMT1 regulatory network can affect STZ-induced cell viability, oxidative stress, and insulin secretion in INS-l cells, which can further impact the progression of diabetes.