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Ubiquitin-specific protease 7 as a potential therapeutic target in dogs with hematopoietic malignancies
Aleksandra Pawlak1, Joanna Bajzert2, Katarzyna Bugiel1
1Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.
Background:
Ubiquitin-specific protease 7 (USP7) belongs to the group of deubiquitinating enzymes (DUBs), which remove ubiquitin which controls various cellular processes such as chromosome segregation, DNA repair, gene expression, protein localization, kinase activity, protein degradation, cell cycle progression, and apoptosis. It is critical for several important functions in the cell, and therefore dysregulation of USP7 can contribute to tumorigenesis.
Objectives:
Alterations in the USP7 protein have been identified in various malignancies of humans. Our aim was to examine whether USP7 could be a potential therapeutic target in hematopoietic cancers of dogs.
Methods:
The expression level of USP7 in lymphocytes from healthy dogs and canine lymphoma cells was determined, and the effect of USP7 inhibition on the vital functions of canine cancer cells was examined.
Results:
We showed that USP7 was overexpressed in lymphomas in dogs. The USP7 inhibitor P5091 has selective cytotoxic activity in canine lymphoma and leukemia cell lines. Our results indicate that inhibition of USP7 leads to a disruption of cell cycle progression, and triggers DNA damage and apoptosis. The observed proapoptotic effect of the USP7 inhibitor most likely is not dependent on the p53 pathway.
Conclusions And Clinical Importance:
Our results suggest that USP7 could be explored as a potential therapeutic target in dogs with lymphoma. The effectiveness of USP7 inhibition in malignant cells is predicted to be independent of their p53 status.
Insights
Ubiquitin-specific protease 7 (USP7) is overexpressed in canine lymphomas. Inhibiting USP7 shows selective toxicity in canine cancer cells, disrupting cell cycle and inducing apoptosis, suggesting USP7 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Veterinary Medicine
Background:
- Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme (DUB) crucial for cellular processes.
- USP7 dysregulation is implicated in tumorigenesis.
- USP7 alterations are observed in human malignancies.
Purpose of the Study:
- To investigate USP7 as a potential therapeutic target in canine hematopoietic cancers.
- To examine USP7 expression and the effects of its inhibition in canine lymphoma.
Main Methods:
- Determined USP7 expression levels in healthy canine lymphocytes and canine lymphoma cells.
- Assessed the impact of USP7 inhibition on canine cancer cell viability and function.
- Utilized the USP7 inhibitor P5091.
Main Results:
- USP7 was found to be overexpressed in canine lymphomas.
- The USP7 inhibitor P5091 demonstrated selective cytotoxic effects on canine lymphoma and leukemia cell lines.
- USP7 inhibition disrupted cell cycle progression, induced DNA damage, and triggered apoptosis.
- The proapoptotic effect was largely independent of the p53 pathway.
Conclusions:
- USP7 represents a promising therapeutic target for canine lymphoma.
- USP7 inhibition is effective in malignant cells regardless of p53 status.
- Further exploration of USP7 as a therapeutic strategy in canine lymphoma is warranted.
