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Ubiquitin specific peptidase 37 and PCNA interaction promotes osteosarcoma pathogenesis by modulating replication
Ravi Chauhan1, Ashna Gupta1, Lakshay Malhotra2
1Department of Medical Oncology (Lab), Dr. BRAIRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, Delhi, 110029, India.
Journal of Translational Medicine
|April 29, 2023
Summary
Ubiquitin-specific peptidase 37 (USP37) promotes survival in osteosarcoma by enhancing replication stress tolerance. Targeting the USP37-PCNA interaction may offer a novel therapeutic strategy for bone cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma affects young individuals and is characterized by genetic alterations leading to metastasis.
- Ubiquitin-specific peptidases (USPs) are crucial regulators of cellular processes, with USP37 implicated in replication stress and oncogenesis.
Purpose of the Study:
- To investigate the role of USP37 in osteosarcoma progression and its interaction with PCNA.
- To explore USP37 as a potential therapeutic target for osteosarcoma.
Main Methods:
- Analysis of TCGA database for USP37 expression and patient survival.
- RNA sequencing to assess gene expression changes upon USP37 modulation.
- Molecular assays (colony formation, immunofluorescence, IP, DNA replication restart) to study USP37-PCNA interaction.
- Immunohistochemistry on patient tissues to correlate USP37 and PCNA expression.
Main Results:
- Increased USP37 expression correlates with decreased progression-free survival in osteosarcoma.
- USP37 overexpression enhances cell survival and DNA damage repair, while depletion increases sensitivity to replication stress.
- USP37 physically interacts with PCNA, influencing replication stress response.
Conclusions:
- USP37 promotes replication stress tolerance in osteosarcoma cells via PCNA interaction.
- Disrupting the USP37-PCNA interaction could induce synthetic lethality in osteosarcoma.
- USP37 is a potential therapeutic target for osteosarcoma.
Keywords:
Deubiquitinating enzymesMetastasisProliferating cell nuclear antigenReplication stressUbiquitin specific protease 37More Related Videos
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