Abstract
Lung cancer, one of the most prevalent and lethal malignancies in clinical practice, is characterized by high incidence and mortality, and poor prognosis. Cuproptosis, a recently identified form of cell death, has emerged as a focal point in tumor diagnosis and therapy. To elucidate the role of cuproptosis in lung cancer progression and identify potential therapeutic agents, we employed bioinformatics approaches to analyze public databases, aiming to uncover key copper-related genes and pathways associated with lung cancer. Using the GSE21933 dataset, we identified 2,892 differentially expressed genes (DEGs) in lung cancer, comprising 1,369 upregulated and 1,523 downregulated genes. By intersecting these DEGs with cuproptosis-related genes, we identified three hub genes (CDK1, FOXM1, and PRC1) using VM, random forest, and MCODE algorithms. Targeted drug prediction using the DsigDB module of the Enrichr website revealed LUCANTHONE as the top candidate. Western blot, RT-qPCR, and immunofluorescence analyses confirmed that CDK1, FOXM1, and PRC1 were highly expressed at both protein and mRNA levels in lung cancer tissues and cells. Treatment of A549 lung cancer cells with LUCANTHONE resulted in decreased expression of CDK1, FOXM1, and PRC1, reduced cell proliferation and invasiveness, and increased apoptosis. Our findings demonstrate that CDK1, FOXM1, and PRC1 are critical components of the cuproptosis pathway in lung cancer, and LUCANTHONE may serve as a promising therapeutic agent for inhibiting their expression and suppressing lung cancer progression.