miR-215-5p aggravates severe acute pancreatitis by inhibiting SLC7A11 to induce ferroptosis

Severe acute pancreatitis (AP) is accompanied by systemic inflammatory process and organ dysfunction. Emerging evidence suggests that miRNA contributes to pancreatic injury. This study investigated miR-215-5p in AP and its mechanistic insight. 100 healthy controls and 130 patients with AP were enrolled. Based on disease severity, AP is classified into 72 mild acute pancreatitis (MAP) and 58 non-MAP (NMAP). Serum miR-215-5p abundance was quantified by qRT-PCR. The clinical significance was evaluated by logistic regression and ROC curve. A caerulein (CAE)-induced injury model was established in AR42J pancreatic acinar cells. Functional experiments, including cell viability, LDH release, and oxidative stress indicators, were performed. The RNA interaction was validated by dual-luciferase assay. miR-215-5p was elevated in AP and NMAP subjects. miR-215-5p positively correlated with BISAP score. miR-215-5p exhibits strong performance in distinguishing NMAP from MAP. Multivariate analysis identified miR-215-5p as an independent risk factor for NMAP. In vitro, CAE treatment upregulated miR-215-5p and induced ferroptosis, as substantiated by the accumulation of Fe²⁺, ROS, and MDA and decreased GSH and GPX4 expression. Inhibition of miR-215-5p alleviated cellular injury, including suppressed ferroptosis, and reduced inflammatory cytokine production. miR-215-5p directly binds to SLC7A11. SLC7A11 silencing reversed the protective role of miR-215-5p inhibition on AR42J cells. miR-215-5p is elevated and associated with disease severity. miR-215-5p may promotes pancreatic acinar cell injury by targeting SLC7A11 and inducing ferroptosis. Not applicable.