ArticleCell death & disease2023
USP22 upregulates ZEB1-mediated VEGFA transcription in hepatocellular carcinoma.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Role of ZEB1 in angiogenesis and therapeutic potential (Review).International journal of molecular medicine · 2026Review
- PKM2 Lactylation Promotes Colorectal Cancer Vasculogenic Mimicry and Bevacizumab Resistance by Facilitating FOSL1 Super-enhancer Formation.Cancer research · 2026Article
- The role of e3 ubiquitin ligases and deubiquitinating enzymes in hepatocellular carcinoma.Cell biology and toxicology · 2026Review
- Targeting USP22 reprograms the tumor microenvironment and sensitizes KRAS/p53-driven lung cancer to anti-PD-1 immunotherapy.Theranostics · 2026Article
- Epithelial to Mesenchymal Transition Transcriptional Regulator ZEB1 in Liver Cancer: Oncogenic Roles and Therapeutic Potential.International journal of molecular sciences · 2025Review
- ZEB1 and Uveal Melanoma Invasiveness.International journal of molecular sciences · 2025Article
- VRK2 targeting potentiates anti-PD-1 immunotherapy in hepatocellular carcinoma through MYC destabilization.Nature communications · 2025Article
- Article
- A positive feedback loop of SRSF9/USP22/ZEB1 promotes the progression of ovarian cancer.Cancer biology & therapy · 2024Article
- Disrupting USP39 deubiquitinase function impairs the survival and migration of multiple myeloma cells through ZEB1 degradation.Journal of experimental & clinical cancer research : CR · 2024Article
- Roles of deubiquitinases in urologic cancers (Review).Oncology letters · 2024Review
- The decrease in zinc-finger E-box-binding homeobox-1 could accelerate steroid-induced osteonecrosis of the femoral head by repressing type-H vessel formation via Wnt/β-catenin pathway.Animal models and experimental medicine · 2024Article
- [Sphingosine kinase-1 regulates migration and invasion of gastric cancer cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Ubiquitin-specific protease 21 promotes tumorigenicity and stemness of colorectal cancer by deubiquitinating and stabilizing ZEB1.World journal of gastrointestinal oncology · 2024Article
- USP22 supports the aggressive behavior of basal-like breast cancer by stimulating cellular respiration.Cell communication and signaling : CCS · 2024Article
- USP32 deubiquitinase: cellular functions, regulatory mechanisms, and potential as a cancer therapy target.Cell death discovery · 2023Review
- Modeling of senescence-related chemoresistance in ovarian cancer using data analysis and patient-derived organoids.Frontiers in oncology · 2023Article
- ZEB1 Fuels Serine Metabolism to Promote HCC Metastasis.Cellular and molecular gastroenterology and hepatology · 2023Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is a common solid tumor with high rate of recurrence and mortality. Anti-angiogenesis drugs have been used for the therapy of HCC. However, anti-angiogenic drug resistance commonly occurs during HCC treatment. Thus, identification of a novel VEGFA regulator would be better understanding for HCC progression and anti-angiogenic therapy resistance. Ubiquitin specific protease 22 (USP22) as a deubiquitinating enzyme, participates in a variety of biological processes in numerous tumors. While the molecular mechanism underlying the effects of USP22 on angiogenesis is still needed to be clarified. Here, our results demonstrated that USP22 acts as a co-activator of VEGFA transcription. Importantly, USP22 is involved in maintenance of ZEB1 stability via its deubiquitinase activity. USP22 was recruited to ZEB1-binding elements on the promoter of VEGFA, thereby altering histone H2Bub levels, to enhance ZEB1-mediated VEGFA transcription. USP22 depletion decreased cell proliferation, migration, Vascular Mimicry (VM) formation, and angiogenesis. Furthermore, we provided the evidence to show that knockdown of USP22 inhibited HCC growth in tumor-bearing nude mice. In addition, the expression of USP22 is positively correlated with that of ZEB1 in clinical HCC samples. Our findings suggest that USP22 participates in the promotion of HCC progression, if not all, at least partially via up-regulation of VEGFA transcription, providing a novel therapeutic target for anti-angiogenic drug resistance in HCC.
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