KCNJ2-AS1 Drives Inflammation and Ferroptosis via the miR-212-3p/EGR1 Axis in Sepsis-Associated Acute Lung Injury.

Sepsis-associated acute lung injury (SALI) is a severe complication of sepsis, characterized by excessive inflammation and high mortality. Ferroptosis, an iron-dependent form of cell death, has been implicated in the pathogenesis of SALI. This study investigates the role of lncRNA KCNJ2-AS1 in SALI, focusing on its regulation of ferroptosis and inflammatory responses. Differential expression analysis identified KCNJ2-AS1 as upregulated in sepsis patients. KCNJ2-AS1 expression was measured by RT-qPCR in 115 SALI patients and controls. Its association with inflammatory markers and prognostic value for 28-day prognosis were further evaluated. The effects of KCNJ2-AS1 on ferroptosis markers and ROS levels were examined in HPAEpiC cells using in vitro experiments. The involvement of the KCNJ2-AS1/miR-212-3p/EGR1 axis was explored using dual-luciferase assays and functional studies. KCNJ2-AS1 was overexpressed in SALI patients, correlating with increased inflammatory cytokines and reduced survival. In vitro, KCNJ2-AS1 induced ferroptosis, increasing ROS and Fe²⁺ levels while downregulating GPX4 and upregulating ACSL4. Ferroptosis inhibition Fer-1 reversed these effects. Additionally, KCNJ2-AS1 regulated the miR-212-3p/EGR1 axis, modulating inflammation and ferroptosis in the LPS-induced SALI model. KCNJ2-AS1 may promote SALI pathogenesis by regulating ferroptosis and inflammation via the miR-212-3p/EGR1 axis, emerging as a potential biomarker and therapeutic target.