ArticleCell death and differentiation2021
Deubiquitinase USP39 and E3 ligase TRIM26 balance the level of ZEB1 ubiquitination and thereby determine the progression of hepatocellular carcinoma.
Article in Cell death and differentiation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 2 of them syntheses that pooled it.
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Who cites it
101 citing papers in PubMed, 2 syntheses or guidelines pooled it, 145 citations in OpenAlex.
- Clinicopathological and Prognostic Significance of Ubiquitin-Specific Protease 39 Overexpression in solid Cancers: A Meta-Analysis.Asian Pacific journal of cancer prevention : APJCP · 2023Pooled it
- [Advances of TRIM superfamily proteins in chronic liver disease and hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Pooled it
- MYC-Mediated USP39 Upregulation Stabilizes SRSF1 in Pancreatic Cancer.Molecular cancer research : MCR · 2026Article
- TRIM26 triggers ferroptosis via ZEB1 degradation to suppress nasopharyngeal carcinoma progression.Journal of molecular histology · 2026Article
- Deubiquitinating Enzymes as Therapeutic Candidates in Hepatocellular Carcinoma and Other Liver Disease.International journal of molecular sciences · 2026Review
- USP39 promotes antiviral defense through post-transcriptional control of RIG-I and stabilization of STING.PLoS biology · 2026Article
- Pancancer Fine-Mapping of Mutational Intolerance Identifies CHEK1 as an Immunosuppressive Driver in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrating machine learning and spatial transcriptomics uncovers shared immunomodulatory deubiquitinases in MAFLD and HCC.Human genetics · 2026Article
- HDAC7 aggravates malignant proliferation of hepatocellular carcinoma cells via the TRIM26/CBX4 axis.Molecular genetics and genomics : MGG · 2026Article
- UBE2M as a bridge spanning neddylation and cell cycle regulation in colorectal adenocarcinoma.Experimental & molecular medicine · 2026Article
- Suppressing SMURF1 to preserve GSTM2: An approach to reducing gastric cancer aggressivenessHistology and histopathology · 2026Article
- TRIM26-mediated regulation of TRAF6 ubiquitination enhances host immune response during Toxoplasma gondii infection.Cellular and molecular life sciences : CMLS · 2026Article
- A Stable Bioisostere of Ester-Linked Ubiquitin Chains Enables Decoding of Protein Interactors.Chembiochem : a European journal of chemical biology · 2026Article
- Epigenetic alterations in cancer metastasis: molecular mechanisms and implications for precision oncology.Frontiers in oncology · 2026Review
- TRIM26 deficiency drives gastric cancer lymph node metastasis via TGF-β signaling activation and modulates gemcitabine response.Frontiers in cell and developmental biology · 2026Article
- Inhibition of the PI3K/AKT signaling pathway blocks the oncogenic activity of TRIM26 in prostate cancer cells.Asian journal of andrology · 2026Article
- Transcriptomic Analysis Reveals the Role ofHuman mutation · 2026Article
- Splicing as an integrative layer linking cell cycle regulation, epigenetic dynamics, and environmental responses in plants.Frontiers in plant science · 2026Review
- Ubiquitin-specific protease 5 promotes breast cancer progression by stabilizing Forkhead box M1 through deubiquitination.CytoJournal · 2026Article
- TRIM47-facilitated PLK1 stabilization promotes the proliferation of liver cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2025Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Emerging evidence suggests that USP39 plays an important role in the development of hepatocellular carcinoma (HCC). However, the molecular mechanism by which USP39 promotes HCC progression has not been well defined, especially regarding its putative ubiquitination function. Zinc-finger E-box-binding homeobox 1 (ZEB1) is a crucial inducer of epithelial-to-mesenchymal transition (EMT) to promote tumor proliferation and metastasis, but the regulatory mechanism of ZEB1 stability in HCC remains enigmatic. Here, we reveal that USP39 is highly expressed in human HCC tissues and correlated with poor prognosis. Moreover, USP39 depletion inhibits HCC cell proliferation and metastasis by promoting ZEB1 degradation. Intriguingly, deubiquitinase USP39 has a direct interaction with the E3 ligase TRIM26 identified by co-immunoprecipitation assays and immunofluorescence staining assays. We further demonstrate that TRIM26 is lowly expressed in human HCC tissues and inhibits HCC cell proliferation and migration. TRIM26 promotes the degradation of ZEB1 protein by ubiquitination in HCC. Deubiquitinase USP39 and E3 ligase TRIM26 function in an antagonistic pattern, but not a competitive pattern, and play key roles in controlling ZEB1 stability to determine the HCC progression. In summary, our data reveal a previously unknown mechanism that USP39 and TRIM26 balance the level of ZEB1 ubiquitination and thereby determine HCC cell proliferation and migration. This novel mechanism may provide new approaches to target treatment for inhibiting HCC development by restoring TRIM26 or suppressing USP39 expression in HCC cases with high ZEB1 protein levels.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.