Open Access

ARTICLE

UCK2 Drives Lung Adenocarcinoma Progression and Immune Dysregulation via the RHEB/mTOR Signaling Axis

Xiaolin Wei^1,2, Jing Guo¹, Chuntao Tao³, Yong Bao², Li Yang^1,*, Hong Chen^1,*

1 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
2 Department of Respiratory Medicine, Sichuan Taikang Hospital, Chengdu, China
3 Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, China

* Corresponding Authors: Li Yang. Email: ; Hong Chen. Email:

(This article belongs to the Special Issue: Identification of potential targets and biomarkers for cancers and the exploration of novel molecular mechanisms of tumorigenesis and metastasis)

Oncology Research 2026, 34(6), 26 https://doi.org/10.32604/or.2026.078651

Received 05 January 2026; Accepted 17 March 2026; Issue published 21 May 2026

Abstract

Objectives: 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. Methods: 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. In vitro 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. Results: 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. Conclusion: 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.

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Supplementary Material

Supplementary Material File

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