TY  - EJOU
AU  - Wei, Xiaolin 
AU  - Guo, Jing 
AU  - Tao, Chuntao 
AU  - Bao, Yong 
AU  - Yang, Li 
AU  - Chen, Hong 

TI  - UCK2 Drives Lung Adenocarcinoma Progression and Immune Dysregulation via the RHEB/mTOR Signaling Axis
T2  - Oncology Research

PY  - 
VL  - 
IS  - 
SN  - 1555-3906

AB  - <b>Objectives:</b> Uridine-cytidine kinase 2 (UCK2) plays a crucial role in the pyrimidine salvage pathway, but its function in lung adenocarcinoma (LUAD) is still largely unclear. The study aimed to investigate the expression, prognostic value, biological functions, and molecular mechanisms of UCK2 in LUAD. <b>Methods:</b> Bioinformatic analyses were performed using The Cancer Genome Atlas (TCGA), Gene Set Cancer Analysis (GSCA), Gene Expression Omnibus (GEO), and Genotype Tissue Expression (GTEx) datasets. <i>In vitro</i> assays evaluated the effect of UCK2 overexpression on LUAD cells. Co-immunoprecipitation and pathway analyses were utilized to explore the underlying mechanism. Immune landscape and drug sensitivity analyses were also carried out. <b>Results:</b> UCK2 was markedly upregulated in LUAD tissues, correlating with advanced tumor stage and poor overall survival, and served as an independent prognostic factor. Functionally, overexpression of UCK2 increased the proliferation and migration of LUAD cells. Mechanistically, UCK2 interacted with the small GTPase Ras homolog enriched in brain (RHEB) and regulated the mechanistic target of rapamycin (mTOR) signaling pathway. UCK2 expression was also associated with specific immune profiles and drug sensitivity in LUAD. <b>Conclusion:</b> UCK2 acts as a prognostic indicator and oncogene in LUAD, at least partly via the RHEB/mTOR axis. Targeting UCK2 may represent a promising therapeutic approach for LUAD.
KW  - Uridine-cytidine kinase 2 (UCK2); lung adenocarcinoma (LUAD); prognostic biomarker; RHEB/mTOR signaling; drug sensitivity

DO  - 10.32604/or.2026.078651