ArticleActa pharmacologica Sinica2023
Targeting proteasomal deubiquitinases USP14 and UCHL5 with b-AP15 reduces 5-fluorouracil resistance in colorectal cancer cells.
Article in Acta pharmacologica Sinica, 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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18 citing papers in PubMed, 20 citations in OpenAlex.
- Metabolic reprogramming in colorectal cancer: Mechanisms and therapeutic insights.Genes & diseases · 2027Review
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- Emerging regulatory model of Ubiquitin-Specific Proteases 14 in cancer: from canonical oncogenesis to TME modulation, therapeutic resistance, and non-canonical activities.Journal of translational medicine · 2026Review
- b-AP15 enhances TRAIL-induced cell death in HNSCC via the induction of ROS/JNK/DR5 signalling.Cancer gene therapy · 2026Article
- Disrupting USP14-mediated PARP1 dynamics reinstates MIC-A/B-driven antigen-independent CD8Science advances · 2026Article
- BAP1-mediated stabilization of SUFU enhances E2F1 activity and promotes colorectal tumorigenesis.Cell communication and signaling : CCS · 2026Article
- Modulation of the tumor microenvironment by the ubiquitin-proteasome system in colorectal cancer.Journal of translational medicine · 2025Review
- Identification of AKOS, a Chikungunya virus inhibitor, as a USP14 inhibitor for colorectal cancer treatment.Acta pharmacologica Sinica · 2025Article
- Combination of B-AP15 and HSP90 inhibitor tanespimycin induces ROS-mediated cytotoxicity in human lung cancer cells.BMC pharmacology & toxicology · 2025Article
- Targeting metalloptosis in tumor therapy: from molecular mechanisms to application of metal nanoparticles.Molecular cancer · 2025Review
- B-AP15 inhibited colon cancer cell proliferation by decreasing CDK6, Cyclin A, Cyclin E, c-Myc, and VEGF gene expression.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- USP14 and UCHL5 synergistically deubiquitinate PKCα and translocate NF-κB to promote the progression of anaplastic thyroid cancer.Cell death & disease · 2025Article
- Effect of deubiquitinases in head and neck squamous cell carcinoma (Review).Oncology letters · 2025Review
- USP14/S100A11 axis promote colorectal cancer progression by inhibiting cell senescence.Cell death & disease · 2025Article
- USP39 at the crossroads of cancer immunity: regulating immune evasion and immunotherapy response through RNA splicing and ubiquitin signaling.Frontiers in immunology · 2025Review
- Comprehensive pan-cancer analysis indicates UCHL5 as a novel cancer biomarker and promotes cervical cancer progression through the Wnt signaling pathway.Biology direct · 2024Article
- UCHL5 is a putative prognostic marker in renal cell carcinoma: a study of UCHL family.Molecular biomedicine · 2024Article
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-Fluorouracil (5-FU) is the first-line treatment for colorectal cancer (CRC) patients, but the development of acquired resistance to 5-FU remains a big challenge. Deubiquitinases play a key role in the protein degradation pathway, which is involved in cancer development and chemotherapy resistance. In this study, we investigated the effects of targeted inhibition of the proteasomal deubiquitinases USP14 and UCHL5 on the development of CRC and resistance to 5-FU. By analyzing GEO datasets, we found that the mRNA expression levels of USP14 and UCHL5 in CRC tissues were significantly increased, and negatively correlated with the survival of CRC patients. Knockdown of both USP14 and UCHL5 led to increased 5-FU sensitivity in 5-FU-resistant CRC cell lines (RKO-R and HCT-15R), whereas overexpression of USP14 and UCHL5 in 5-FU-sensitive CRC cells decreased 5-FU sensitivity. B-AP15, a specific inhibitor of USP14 and UCHL5, (1-5 μM) dose-dependently inhibited the viability of RKO, RKO-R, HCT-15, and HCT-15R cells. Furthermore, treatment with b-AP15 reduced the malignant phenotype of CRC cells including cell proliferation and migration, and induced cell death in both 5-FU-sensitive and 5-FU-resistant CRC cells by impairing proteasome function and increasing reactive oxygen species (ROS) production. In addition, b-AP15 inhibited the activation of NF-κB pathway, suppressing cell proliferation. In 5-FU-sensitive and 5-FU-resistant CRC xenografts nude mice, administration of b-AP15 (8 mg·kg
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