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CDC25A Promotes Early Metastasis of Lung Adenocarcinoma through Cell Cycle Regulation
Vol 38, Issue 6, 2024
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Abstract
Background: Lung adenocarcinoma (LUAD), a malignant tumor, poses a significant threat to human life, with easy metastasis being the primary reason for its low survival rate. Therefore, this study aimed to identify specific biomarkers and molecular mechanisms underlying early metastasis, providing a solid foundation for developing novel LUAD therapies. Methods: The potential modules associated with LUAD metastasis were analyzed through weighted gene co-expression network analysis, and genes in the key modules were used for functional enrichment. Differentially expressed genes between metastatic and non-metastatic LUAD patients were analyzed using the “limma” package. Blood samples were collected to analyze and validate the expression of target genes. Functional assays were performed to investigate the impacts of cell division cycle 25 A (CDC25A) knockdown on cancer cell proliferation, migration, and cell cycle progression. Results: CDC25A was upregulated in LUAD metastasis, and its overexpression was associated with poorer survival. CDC25A was significantly overexpressed in patients with LUAD metastasis (p < 0.0001). Furthermore, CDC25A knockdown inhibited LUAD cell proliferation (p < 0.01), migration (p < 0.0001), and invasion (p < 0.0001), as well as induced G1 cell cycle arrest. Additionally, suppressing CDC25A expression significantly reduced the expression of cyclin D1 (p < 0.001), cyclin-dependent kinase 4 (CDK4) (p < 0.001), and cyclin-dependent kinase 6 (CDK6) (p < 0.0001). Conclusion: Our findings demonstrate that CDC25A enhances early LUAD metastasis by promoting cell cycle progression. Therefore, targeting CDC25A could be a potential therapeutic approach to suppress metastasis in LUAD patients.
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Copyright (c) 2024 Bin Li, Xuesong Zhao, Haifeng Hu, Tianyu Zhang, Yi Qi, Bo Liu, Bing Lan
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Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy