IDDX18/I Facilitates the Tumorigenesis of Lung Adenocarcinoma by Promoting Cell Cycle Progression through the Upregulation of CDK4

• Published in: International journal of molecular sciences Vol. 25; no. 9
• Main Authors: Feng, Bingbing, Wang, Xinying, Qiu, Ding, Sun, Haiyang, Deng, Jianping, Tan, Ying, Ji, Kaile, Xu, Shaoting, Zhang, Shuishen, Tang, Ce
• Format: Journal Article
• Language: English
• Published: MDPI AG 01.05.2024
• Subjects: Adenocarcinoma; B cells; Biotechnology industry; Cell cycle; Chromatin; Genes; Health aspects; Lung cancer; Prognosis; Protein binding; RNA; RNA sequencing; Tumors; United States; China
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms25094953

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 symbol DDX18), 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 of DDX18 in LUAD tissues and its association with poor patient survival (from public databases). Functional in vivo and in vitro assays revealed that DDX18 knockdown 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 of DDX18. Notably, DDX18 depletion 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 the DDX18 promoter, it did not influence its expression. Collectively, these findings establish DDX18 as a potential oncogene in LUAD, functioning through the CDK4-mediated cell cycle pathway. DDX18 may represent a promising therapeutic target for LUAD intervention.