Integrated Bioinformatic and Experimental Analysis Reveals the Molecular Mechanisms Underlying KDM1B/LSD2 Inhibition as a Therapeutic Strategy in Human Lung Adenocarcinoma.

Abstract

Lung cancer remains a major global health challenge, and the oncogenic function of KDM1B (Lysine-specific Demethylase 1B) is still poorly characterized. This study employed integrated bioinformatics and experimental approaches to investigate KDM1B's function in lung cancer. Pan-cancer analysis using databases such as TIMER revealed notably elevated KDM1B mRNA expression in LUAD datasets, suggesting its potential as a diagnostic biomarker. A strong association was also found between increased KDM1B levels and immune cell infiltration in LUAD datasets. Protein interaction networks constructed using STRING and Cytoscape revealed close associations between KDM1B and key regulatory genes in NSCLC. KEGG enrichment analysis linked KDM1B to the mTOR signaling, which is critical for cell proliferation and survival. RT-PCR and western blotting for experimental validation showed KDM1B expression was significantly increased in A549 and NCI-H460 lung cancer cells. The deletion of KDM1B inhibits cell growth, induces G0/G1 phase cell cycle arrest, and promotes apoptosis in A54 cells. Moreover, cell proliferation was significantly inhibited by the KDM1B inhibitor, tranylcypromine, and induced G0/G1 phase cell cycle arrest, increased apoptosis, ROS, and glycolytic activity in A549 cells. Collectively, these findings highlight KDM1B as a valuable therapeutic target in lung adenocarcinoma and emphasize its key role in lung cancer development.