DDX18 Facilitates the Tumorigenesis of Lung Adenocarcinoma by Promoting Cell Cycle Progression through the Upregulation of CDK4

Lung adenocarcinoma (LUAD) is the most prevalent and aggressive subtype of lung cancer, exhibiting a dismal prognosis with a five-year survival rate below 5%. DEAD-box RNA helicase 18 (DDX18, gene symbolDDX18), a crucial regulator of RNA metabolism, has been implicated in various cellular processes, including cell cycle control and tumorigenesis. However, its role in LUAD pathogenesis remains elusive. This study demonstrates the significant upregulation ofDDX18in LUAD tissues and its association with poor patient survival (from public databases). Functional in vivo and in vitro assays revealed thatDDX18knockdown potently suppresses LUAD progression. RNA sequencing and chromatin immunoprecipitation experiments identified cyclin-dependent kinase 4 (CDK4), a cell cycle regulator, as a direct transcriptional target ofDDX18. Notably,DDX18depletion induced G1 cell cycle arrest, while its overexpression promoted cell cycle progression even in normal lung cells. Interestingly, while the oncogenic protein c-Myc bound to theDDX18promoter, it did not influence its expression. Collectively, these findings establishDDX18as a potential oncogene in LUAD, functioning through the CDK4-mediated cell cycle pathway.DDX18may represent a promising therapeutic target for LUAD intervention.

文章引用产品列表