ArticleClinical and molecular hepatology2024
UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL.
Article in Clinical and molecular hepatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Ubiquitin E3 ligase MYCBP2 targets KIF14 and contributes to acute myeloid leukemia progression.The Journal of biological chemistry · 2026Article
- The UBE2/E2 ubiquitin-conjugating enzyme family at the interface of tumor biology and antitumor immunity: mechanisms, biomarkers, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Article
- Ubiquitin-conjugating Enzymes in Cancer.International journal of biological sciences · 2026Review
- UBE2W promotes pancreatic cancer progression through regulating K63-linked ubiquitination of p53.American journal of cancer research · 2026Article
- Correspondence to editorial on "Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway".Clinical and molecular hepatology · 2026Article
- Network pharmacology and molecular docking to explore the potential mechanism of Codonopsis pilosula delaying aging.Medicine · 2025Article
- The Ubiquitin Script: writing protein fates in chains.Essays in biochemistry · 2025Review
- UBE2S-mediated deubiquitination of GLUT1 via USP10 regulates glucose metabolic reprogramming and immune microenvironment to promote fibrosis in endometriosis.Journal of translational medicine · 2025Article
- Mechanisms of ferroptosis in primary hepatocellular carcinoma and progress of artificial intelligence-based predictive modeling in hepatocellular carcinoma.World journal of gastroenterology · 2025Review
- Post-translational modifications in hepatocellular carcinoma: mechanisms and therapeutic potential.Medical oncology (Northwood, London, England) · 2025Review
- SNORA74A Drives Self-Renewal of Liver Cancer Stem Cells and Hepatocarcinogenesis Through Activation of Notch3 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- High mobility group protein N2 inhibits the progression of hepatocellular carcinoma and the related molecular mechanisms.Cytotechnology · 2025Article
- UBE2S: A novel driver of HIF-1alpha-induced metabolic reprogramming in hepatocellular carcinoma: Editorial on "UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL".Clinical and molecular hepatology · 2025Article
- Stemness- and hypoxia-based prognostic stratification index reveals G6PD as a regulator of hypoxia-driven stemness in hepatocellular carcinoma.Frontiers in immunology · 2025Article
- Correspondence to letter to the editor 1 on "Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma".Clinical and molecular hepatology · 2025Article
- UBE2V1 Promotes Hepatocellular Carcinoma Progression by Forming a Positive Feedback Loop with HIF-1α.Research (Washington, D.C.) · 2025Article
- Correspondence to editorial on "UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL".Clinical and molecular hepatology · 2025Article
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Authors and funding
18 authors.
Funding
Abstract
BACKGROUND/
aimsUbiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking.
methodsCox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth.
resultsBased on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy.
conclusionUBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.
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