YBX1 contributes to lung adenocarcinoma progression and is associated with ferroptosis-related changes via the PI3K/AKT/mTOR pathway

This study aimed to elucidate the role of YBX1 in lung adenocarcinoma (LUAD). YBX1 was highly expressed in LUAD cells, particularly A549; therefore, this study focused on experiments in the A549 cell line, with all experiments conducted in this cell line. YBX1 knockdown via shRNA markedly inhibited cell proliferation, migration, and invasion. Silencing YBX1 resulted in changes consistent with Ferroptosis, as evidenced by increased MDA and Fe²⁺ levels, decreased GSH, increased ROS accumulation and lipid peroxidation, as well as the downregulation of GPX4 and SLC7A11. Mechanistically, YBX1 activated the PI3K/Akt/mTOR pathway, which was suppressed by its knockdown and partially restored by EGF treatment. Treatment with the PI3K Inhibitor LY294002 produced changes consistent with those observed upon YBX1 silencing. In a subcutaneous xenograft mouse model, YBX1 silencing was associated with reduced tumor growth and ferroptosis-related changes, effects that were partially reversed by EGF treatment. These findings suggest that YBX1 is associated with ferroptosis-related changes and altered proliferation and migration in A549 cells, potentially involving PI3K/Akt/mTOR signaling, highlighting YBX1 as a potential therapeutic target.

Ferroptosis; Lung adenocarcinoma; PI3K/AKT/mTOR pathway; Targeted regulation; YBX1.