Mechanism of CircBbs9 in Lung Epithelial Cell Ferroptosis in Lipopolysaccharide-Induced Acute Lung Injury

Acute lung injury (ALI) is an acute inflammatory disorder characterized by damage to alveolar epithelium and vascular endothelium. This study explores the mechanism of CircBbs9 (hsa_circ_0079812) in LPS-induced ALI through ferroptosis, aiming to find new therapies for ALI. LPS-induced ALI mouse models and cell models were established. Lung tissue damage was detected via the wet/dry weight ratio of lung tissues, oxygenation index, and histological injury scoring. MDA, GSH, and inflammatory factor levels were evaluated by ELISA. Fe²⁺ content, intracellular ROS, and lipid ROS were detected. CircBbs9, Cblb, ACSL4, GPX4, and miR-671-5p levels were assessed by qRT-PCR and Western blot. CircBbs9 expression was elevated in LPS-induced mouse and cell models. CircBbs9 knockdown reduced pulmonary pathological injury, alleviated ferroptosis, increased cell viability, and reduced ACSL4 expression. CircBbs9 bound to HuR, thereby inhibiting Cblb expression, and decreasing Cblb-mediated ubiquitination and degradation of ACSL4. CircBbs9 competitively bound to miR-671-5p, thereby upregulating ACSL4 expression. Cblb knockdown or miR-671-5p inhibition reversed the suppressive function of CircBbs9 knockdown on ferroptosis in lung epithelial cells. Simultaneous overexpression of HuR and miR-671-5p has superior inhibitory effects on ferroptosis than their individual overexpression. In conclusion, CircBbs9 promotes lung epithelial cell ferroptosis in LPS-induced ALI via the HuR/Cblb/ACSL4 and miR-671-5p/ACSL4 axes.