FOXM1 Promotes Non-Small Cell Lung Cancer Progression by Increasing CHEK1 Expression.

Abstract

Objective: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-associated mortality. This study aimed to investigate the role of checkpoint kinase 1 (CHEK1) in NSCLC progression and its regulatory relationship with forkhead box protein M1 (FOXM1).

Methods: Transwell assays were used to evaluate the migration and invasion capabilities of NSCLC cells with either CHEK1 overexpression or knockdown. The expression of epithelial-mesenchymal transition (EMT) markers in NSCLC cells under CHEK1 overexpression or knockdown conditions was analyzed via Western blotting. Proliferative capacity was assessed using CCK-8 assays in NSCLC cells with modulated CHEK1 expression. Additionally, real-time quantitative PCR was employed to measure CHEK1 and FOXM1 expression levels in NSCLC tissues. The effects of CHEK1 knockdown on tumor growth were further validated in animal models. The binding of FOXM1 to the CHEK1 promoter region was examined using dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays.

Results: FOXM1 and CHEK1 were upregulated in NSCLC tissues. CHEK1 overexpression promoted NSCLC cell proliferation, while its knockdown suppressed proliferation, inhibited EMT, and reduced tumor growth in vivo. FOXM1 was shown to directly bind to CHEK1 promoter, thereby upregulating CHEK1 expression.

Conclusion: CHEK1 promotes NSCLC cell proliferation and tumor growth, and its expression is regulated by FOXM1. These findings suggest CHEK1 and FOXM1 are potential therapeutic targets for NSCLC treatment.