AKR1C2 silencing promotes ferroptosis and inhibits proliferation, migration, and invasion in lung cancer cells

PMCID: PMC12176218

PMID: 40531841

DOI: 10.1371/journal.pone.0325995

Journal: PloS one

Publication Date: 2025-6-18

Authors: Cui Y, Liu Z

Key Points

• AKR1C2 expression is significantly higher in lung cancer tissues and correlates with worse patient prognosis
• High AKR1C2 expression is associated with increased lymph node metastasis and advanced tumor stages
• Targeted AKR1C2 knockdown demonstrates potential as a therapeutic approach to inhibit lung cancer progression and induce ferroptosis

Summary

This study investigated the role of AKR1C2 in lung adenocarcinoma (LUAD), identifying it as a potential therapeutic target with significant implications for cancer progression. Using bioinformatics analysis and experimental approaches, researchers demonstrated that AKR1C2 is overexpressed in lung cancer tissues and correlates with poor clinical outcomes, including advanced tumor stages and lymph node metastasis.

The research revealed that AKR1C2 knockdown in A549 lung cancer cells significantly inhibits malignant biological behaviors, including cell proliferation, migration, and invasion. Mechanistically, silencing AKR1C2 promotes ferroptosis by increasing reactive oxygen species, malondialdehyde, and Fe²⁺ levels, suggesting a potential novel therapeutic strategy for lung cancer management.