ArticleCellular & molecular biology letters2022
Targeting uridine-cytidine kinase 2 induced cell cycle arrest through dual mechanism and could improve the immune response of hepatocellular carcinoma.
Article in Cellular & molecular biology letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- Biomimetic Nanomedicine for Senescence-Modulated Immune Activation Enhances Immunotherapy Efficacy in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- UCK2 Drives Lung Adenocarcinoma Progression and Immune Dysregulation via the RHEB/mTOR Signaling Axis.Oncology research · 2026Article
- Article
- Prognostic model for predicting recurrence-free survival in hepatocellular carcinoma using integrated analysis of single-cell RNA-sequencing and bulk RNA-sequencing.Oncology letters · 2025Article
- Immunometabolism: crosstalk with tumor metabolism and implications for cancer immunotherapy.Molecular cancer · 2025Review
- A novel immune-metabolic prognostic model stratifies survival and personalizes therapy in hepatocellular carcinoma.Discover oncology · 2025Article
- Comprehensive multi-omics analysis of nucleotide metabolism: elucidating the role and prognostic significance of UCK2 in bladder cancer.Functional & integrative genomics · 2025Article
- The alternative polyadenylation regulator CFIm25 promotes macrophage differentiation and activates the NF-κB pathway.Cell communication and signaling : CCS · 2025Article
- CircUCK2(2,3) promotes cancer progression and enhances synergistic cytotoxicity of lenvatinib with EGFR inhibitors via activating CNIH4-TGFα-EGFR signaling.Cellular & molecular biology letters · 2025Article
- The Role of Uridine in Health and Disease.Journal of inflammation research · 2025Review
- Uridine-cytidine kinase 2 is correlated with immune, DNA damage repair and promotion of cancer stemness in pan-cancer.Frontiers in oncology · 2025Article
- Identification and validation of icaritin-associated prognostic genes in hepatocellular carcinoma through network pharmacology, bioinformatics analysis, and cellular experiments.Frontiers in immunology · 2025Article
- UCK2 promotes intrahepatic cholangiocarcinoma progression and desensitizes cisplatin treatment by PI3K/AKT/mTOR/autophagic axis.Cell death discovery · 2024Article
- Immune- and metabolism-related gene signature analysis uncovers the prognostic and immune microenvironments of hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2024Article
- A hypoxia-glycolysis-lactate-related gene signature for prognosis prediction in hepatocellular carcinoma.BMC medical genomics · 2024Article
- PPP1R14B as a potential biomarker for the identification of diagnosis and prognosis affecting tumor immunity, proliferation and migration in prostate cancer.Journal of Cancer · 2024Article
- Identification of novel biomarkers, shared molecular signatures and immune cell infiltration in heart and kidney failure by transcriptomics.Frontiers in immunology · 2024Article
- Predictive value of a stemness-based classifier for prognosis and immunotherapy response of hepatocellular carcinoma based on bioinformatics and machine-learning strategies.Frontiers in immunology · 2024Article
- Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance.Cellular & molecular biology letters · 2023Review
- Development and validation of robust metabolism-related gene signature in the prognostic prediction of hepatocellular carcinoma.Journal of cellular and molecular medicine · 2023Article
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundPyrimidine metabolism is critical for tumour progression. Uridine-cytidine kinase 2 (UCK2), a key regulator of pyrimidine metabolism, is elevated during hepatocellular carcinoma (HCC) development and exhibits carcinogenic effects. However, the key mechanism of UCK2 promoting HCC and the therapeutic value of UCK2 are still undefined. The aim of this study is to investigate the potential of UCK2 as a therapeutic target for HCC.
methodsGene expression matrices were obtained from public databases. RNA-seq, co-immunoprecipitation and RNA-binding protein immunoprecipitation were used to determine the mechanism of UCK2 promoting HCC. Immune cell infiltration level and immune-related functional scores were evaluated to assess the link between tumour microenvironment and UCK2.
resultsIn HCC, the expression of UCK2 was upregulated in part by TGFβ1 stimulation. UCK2 promoted cell cycle progression of HCC by preventing the degradation of mTOR protein and maintaining the stability of PDPK1 mRNA. We also identified UCK2 as a novel RNA-binding protein. Downregulation of UCK2 induced cell cycle arrest and activated the TNFα/NFκB signalling pathway-related senescence-associated secretory phenotype to modify the tumour microenvironment. Additionally, UCK2 was a biomarker of the immunosuppressive microenvironment. Downregulated UCK2 induced a secretory phenotype, which could improve the microenvironment, and decreased UCK2 remodelling metabolism could lower the resistance of tumour cells to T-cell-mediated killing.
conclusionsTargeting UCK2 inhibits HCC progression and could improve the response to immunotherapy in patients with HCC. Our study suggests that UCK2 could be an ideal target for HCC.
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