ArticleJournal of experimental & clinical cancer research : CR2021
USP1-dependent RPS16 protein stability drives growth and metastasis of human hepatocellular carcinoma cells.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
- HERC4 synergizes with USP16 to promote lung adenocarcinoma growth by augmenting protein translation via stabilizing RPS15.Oncogene · 2026Article
- CircRPPH1 promotes hepatocellular carcinoma progression through inhibiting PPARα transcription and accelerating its ubiquitination and degradation.Cellular and molecular life sciences : CMLS · 2026Article
- USP1 promotes hepatocellular carcinoma progression by modulating mitophagy via stabilizing MCM3 to regulate the Keap1-Nrf2 axis.iScience · 2026Article
- USP1 driven mitotic dysregulation and PLK1 stabilization confer Lenvatinib resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Genetic and Epigenetic Mechanisms in Serrated Adenocarcinomas and Classical Colorectal Carcinomas: An In Silico Study.Current issues in molecular biology · 2026Article
- Single-cell RNA Sequencing Identifies Prognostic Biomarkers in Extramedullary Multiple Myeloma.Current medicinal chemistry · 2026Article
- Molecular Mechanisms of the Ubiquitin-Specific Proteases (USPs) Family in Biliary Tract Cancer and Targeted Intervention Strategies.Biomedicines · 2025Review
- The other side of the coin: protein deubiquitination by Ubiquitin-Specific Protease 1 in cancer progression and therapy.Future medicinal chemistry · 2025Review
- Ubiquitin-specific protease 1 facilitates tumor immune escape from natural killer cells and predicts the prognosis in small cell lung cancer.Oncology research · 2025Article
- SENP3 mediates deSUMOylation of SIX1 to promote prostate cancer proliferation and migration.Cellular & molecular biology letters · 2024Article
- Ribosomal proteins in hepatocellular carcinoma: mysterious but promising.Cell & bioscience · 2024Review
- Article
- Emerging roles of deubiquitinating enzymes in actin cytoskeleton and tumor metastasis.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- PHGDH: a novel therapeutic target in cancer.Experimental & molecular medicine · 2024Review
- The identification of hub genes associated with pure ground glass nodules using weighted gene co-expression network analysis.BMC pulmonary medicine · 2024Article
- Deubiquitinase USP1 regulates sarbecovirus ORF6 protein function.Journal of virology · 2024Article
- Roles of USP1 in Ewing sarcoma.Genes & cancer · 2024Article
- USP21 deubiquitinates and stabilizes HSP90 and ENO1 to promote aerobic glycolysis and proliferation in cholangiocarcinoma.International journal of biological sciences · 2024Article
- Role of Ubiquitin-specific Proteases in Hepatocellular Carcinoma Pathogenesis.Current topics in medicinal chemistry · 2024Review
- Transcriptomic analysis of hepatocytes reveals the association between ubiquitin-specific peptidase 1 and yes-associated protein 1 during liver regeneration.Regenerative therapy · 2023Article
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) remains a medical challenge due to its high proliferation and metastasis. Although deubiquitinating enzymes (DUBs) play a key role in regulating protein degradation, their pathological roles in HCC have not been fully elucidated.
methodsBy using biomass spectrometry, co-immunoprecipitation, western blotting and immunofluorescence assays, we identify ribosomal protein S16 (RPS16) as a key substrate of ubiquitin-specific peptidase 1 (USP1). The role of USP1-RPS16 axis in the progression of HCC was evaluated in cell cultures, in xenograft mouse models, and in clinical observations.
resultsWe show that USP1 interacts with RPS16. The depletion of USP1 increases the level of K48-linked ubiquitinated-RPS16, leading to proteasome-dependent RPS16 degradation. In contrast, overexpression of USP1-WT instead of USP1-C90A (DUB inactivation mutant) reduces the level of K48-linked ubiquitinated RPS16, thereby stabilizing RPS16. Consequently, USP1 depletion mimics RPS16 deficiency with respect to the inhibition of growth and metastasis, whereas transfection-enforced re-expression of RPS16 restores oncogenic-like activity in USP1-deficient HCC cells. Importantly, the high expression of USP1 and RPS16 in liver tissue is a prognostic factor for poor survival of HCC patients.
conclusionsThese findings reveal a previously unrecognized role for the activation of USP1-RPS16 pathway in driving HCC, which may be further developed as a novel strategy for cancer treatment.
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