Background: Acute pancreatitis (AP) is an inflammatory disease with high mortality. Previous study has suggested that circular RNAs are dysregulated and involved in the regulation of inflammatory responses in AP. This study aimed to investigate the function and regulatory mechanism underlying mmu_circ_0000037 in caerulein-induced AP cellular model.
Methods: Caerulein-treated MPC-83 cells were used as an in vitro cellular model for AP. The expression levels of mmu_circ_0000037, microRNA (miR)-92a-3p, and protein inhibitor of activated STAT1 (Pias1) were detected by quantitative real-time polymerase chain reaction. Cell viability, amylase activity, apoptosis, and inflammatory response were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Amylase Assay Kit, flow cytometry, and enzyme-linked immunosorbent assays. The protein level was quantified by western blot analysis. The target interaction between miR-92a-3p and mmu_circ_0000037 or Pias1 were predicted by StarbaseV3.0 and validated by dual-luciferase reporter assay and RNA immunoprecipitation assay.
Results: Mmu_circ_0000037 and Pias1 levels were decreased, whereas miR-92a-3p expression was elevated in caerulein-induced MPC-83 cells. Overexpression of mmu_circ_0000037 protected MPC-83 cells from caerulein-induced the decrease of cell viability, as well as the promotion of amylase activity, apoptosis and inflammation. MiR-92a-3p was targeted by mmu_circ_0000037, and miR-92a-3p overexpression rescued the effect of mmu_circ_0000037 on caerulein-induced MPC-83 cell injury. Pias1 was confirmed as a target of miR-92a-3p and mmu_circ_0000037 regulated the expression of Pias1 by sponging miR-92a-3p.
Conclusion: Mmu_circ_0000037 relieves caerulein-induced inflammatory injury in MPC-83 cells by targeting miR-92a-3p/Pias1 axis, providing a theoretical basis for the treatment of AP.
Keywords: Pias1; acute pancreatitis; inflammatory injury; miR-92a-3p; mmu_circ_0000037.
© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.