ArticleInternational journal of biological sciences2024
USP21 deubiquitinates and stabilizes HSP90 and ENO1 to promote aerobic glycolysis and proliferation in cholangiocarcinoma.
Article in International journal of biological sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 23 citations in OpenAlex.
- Decoding Treatment Response and Prognosis in Unresectable Locally Advanced Non-Small Cell Lung Cancer by Integrating Spatiotemporal Heterogeneity FromJCO precision oncology · 2026Article
- UFL1-Mediated UFMylation of ENO1 Restrains Aerobic Glycolysis and Colorectal Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- USP21 drives immune evasion in colorectal cancer via deubiquitination and stabilization of β-catenin.Cellular & molecular immunology · 2026Article
- Targeting HIF-1α promotes ferroptosis and boosts antitumor immunity in MSS colorectal cancer.Redox biology · 2026Article
- FBXL6 promotes bladder cancer progression by stabilizing ENO1 through K63-linked ubiquitination.Cell death discovery · 2026Article
- Enolase 1: A paradigm of metabolic enzyme moonlighting in tumorigenesis (Review).International journal of oncology · 2026Review
- Exosomes from tumor-associated macrophages promote glycolysis and malignant NSCLC progression by delivery of hsa_circ_0000896.Biology direct · 2026Article
- PSMD14-mediated PFKFB2 deubiquitination activates H3K27 lactylation to drive cancer stemness in gastric adenocarcinoma.Cell death and differentiation · 2026Article
- CircBARD1 suppresses tumor progression driven by H3K18 lactylation-CCNA2 axis in human bladder cancer.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- The deubiquitinating enzyme UCHL3 promotes bladder cancer progression and glycolysis through enhancing PKM2 protein stability.Frontiers in oncology · 2026Article
- USP25 attenuates the immunosuppressive tumor microenvironment via the deubiquitination of TAB2 in head and neck squamous cell carcinoma.Cell death discovery · 2025Article
- Molecular Mechanisms of the Ubiquitin-Specific Proteases (USPs) Family in Biliary Tract Cancer and Targeted Intervention Strategies.Biomedicines · 2025Review
- Targeting USP21 to inhibit abdominal aortic aneurysm progression by suppressing the phenotypic transition of vascular smooth muscle cells.Cell reports. Medicine · 2025Article
- ARID1A deficiency promotes malignant proliferation of hepatocellular carcinoma by activating HDAC7/ENO1 signaling pathway.Hepatology communications · 2025Article
- Warburg effect and lactylation in cancer: mechanisms for chemoresistance.Molecular medicine (Cambridge, Mass.) · 2025Review
- USP31 Activates the Wnt/β-catenin Signaling Pathway and Promotes Gastric Cancer Cell Proliferation, Invasion and Migration.Recent patents on anti-cancer drug discovery · 2025Article
- Machine Learning-based Macrophage Signature for Predicting Prognosis and Immunotherapy Benefits in Cholangiocarcinoma.Current medicinal chemistry · 2025Article
- EMC2 promotes breast cancer progression and enhances sensitivity to PDK1/AKT inhibition by deubiquitinating ENO1.International journal of biological sciences · 2025Article
- Role of ENO1 and its targeted therapy in tumors.Journal of translational medicine · 2024Review
- Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma.Cancer cell international · 2024Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deubiquitylating enzymes (DUBs) play an essential role in targeted protein degradation and represent an emerging therapeutic paradigm in cancer. However, their therapeutic potential in cholangiocarcinoma (CCA) has not been explored. Herein, based on The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) databases, we found that ubiquitin-specific protease 21 (USP21) was upregulated in CCA, high USP21 level was associated with poor prognosis. In vivo and in vitro, we identified USP21 as a master regulator of CCA growth and maintenance, which directly interacted with deubiquitinates and stabilized the heat shock protein 90 (HSP90) through K48-linked deubiquitination, and in turn, this stabilization increased HIF1A expression, thus upregulating key glycolytic enzyme genes ENO2, ENO3, ALDOC, ACSS2, and then promoted aerobic glycolysis, which provided energy for CCA cell proliferation. In addition, USP21 could directly stabilize alpha-Enolase 1 (ENO1) to promote aerobic glycolysis. Furthermore, increased USP21 level enhanced chemotherapy resistance to the gemcitabine-based regimen. Taken together, we identify a USP21-regulated aerobic glycolysis mechanism that involves the USP21/HSP90/HIF1A axis and USP21/ENO1 axis in CCA tumorigenesis, which could serve as a potential target for the treatment of CCA.
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Registered trials
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