ArticleOncoTargets and therapy2019
Ubiquitin-specific protease 4 promotes glioblastoma multiforme via activating ERK pathway.
Article in OncoTargets and therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implications.Frontiers in epigenetics and epigenomics · 2025Review
- USP4 promotes PTC progression by stabilizing LDHA and activating the MAPK and AKT signaling pathway.Aging · 2024Article
- The TGF-β Family in Glioblastoma.International journal of molecular sciences · 2024Review
- High USP4 mRNA is associated with an HPV-positive status in head and neck squamous cell carcinoma patients.Journal of cancer research and clinical oncology · 2023Article
- USP4 promotes the proliferation and glucose metabolism of gastric cancer cells by upregulating PKM2.PloS one · 2023Article
- Inhibition of Ubiquitin-specific Protease 4 Attenuates Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells via Transforming Growth Factor Beta Receptor Type I.Current medical science · 2022Article
- Binding of Vialinin A andMolecules (Basel, Switzerland) · 2022Article
- The Role of the Ubiquitin Proteasome System in Glioma: Analysis Emphasizing the Main Molecular Players and Therapeutic Strategies Identified in Glioblastoma Multiforme.Molecular neurobiology · 2021Review
- Molecular Mechanisms of DUBs Regulation in Signaling and Disease.International journal of molecular sciences · 2021Review
- Deubiquitinating Enzymes Orchestrate the Cancer Stem Cell-Immunosuppressive Niche Dialogue: New Perspectives and Therapeutic Potential.Frontiers in cell and developmental biology · 2021Review
- Spotlight on USP4: Structure, Function, and Regulation.Frontiers in cell and developmental biology · 2021Review
- The Deubiquitinase USP4 Stabilizes Twist1 Protein to Promote Lung Cancer Cell Stemness.Cancers · 2020Article
- The RNA-Binding Ubiquitin Ligase MEX3A Affects Glioblastoma Tumorigenesis by Inducing Ubiquitylation and Degradation of RIG-I.Cancers · 2020Article
- Targeting the Ubiquitin System in Glioblastoma.Frontiers in oncology · 2020Review
- USP4 function and multifaceted roles in cancer: a possible and potential therapeutic target.Cancer cell international · 2020Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlioblastoma multiforme (GBM) is one of the most common brain tumors in adults. Current treatments cannot increase survival to a large extent, as the glioblastoma development mechanisms remain unknown. It has been well documented that ubiquitination contributes to tumor initiation and/or progression in many kinds of cancer. Ubiquitin-specific protease 4 (USP4), a member of deubiquitinating enzymes (DUBs) family, can remove ubiquitin residues and play a role in cancer development.
methodsIn the current study, lentiviruses were used to manipulate the expression of USP4. Real-time PCR and Western blot were used to measure the expression level of USP4. Then, CCK-8 and annexin-V staining were used to detect cell proliferation and cell apoptosis, respectively.
resultsFirst, we found that USP4 was highly upregulated in GBM tissues in comparison with that in normal tissues and high level of USP4 correlated with poor prognosis. Moreover, knockdown of USP4 could significantly inhibit cell proliferation and increase cell apoptosis in U87 and T98G cells. Cells with stable USP4 reduction exhibited slower tumor growth rate and smaller tumor size than the control group cells in a xenograft mouse model. Inhibition of USP4 downregulated the expression of PCNA, Bcl-2 and p-ERK1/2, but upregulated the expression of Bax both in vitro and in vivo. Inversely, USP4 overexpression could attenuate the effects contributed by ERK inhibitor. TGF-βR inhibition reduced level of TGF-βR1, p-smad2 and p-ERK1/2 which can partially be rescued by USP4 overexpression.
conclusionUSP4, as a potential novel oncogene, promotes GBM by activation of ERK pathway through regulating TGF-β.
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