Loss of NLN suppresses lung cancer progression by inducing ferroptosis through downregulating m⁶A methylation of GPX4.

ABSTRACT: Current targeted therapies for non-small cell lung cancer (NSCLC) face significant limitations, primarily due to the small proportion of patients who respond to existing targets and the development of drug resistance. Consequently, identifying novel therapeutic targets is crucial to overcome these challenges. In this study, we identified Neurolysin (NLN) as a novel therapeutic target for NSCLC using high-throughput proteomics. We validated the oncogenic role of NLN through in vitro cellular models and in vivo studies, and uncovered a previously unrecognized mechanism in ferroptosis regulation. We demonstrated that NLN expression was significantly upregulated in lung cancer tissues relative to adjacent normal tissues. More notably, inhibition of NLN induced ferroptosis in lung cancer cells.

SUBMITTER: Liu L 

PROVIDER: S-EPMC12664413 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature