ArticleJournal of translational medicine2023
Ubiquitin specific peptidase 37 and PCNA interaction promotes osteosarcoma pathogenesis by modulating replication fork progression.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Targeting the METTL3/PCNA axis with STM2457 overcomes cisplatin resistance in osteosarcoma.Translational cancer research · 2025Article
- Targeting ubiquitin-specific protease 14 reduces metastatic potential and metabolic activity in cervical cancer via direct modulation of monocarboxylate transporter-4.Journal of translational medicine · 2025Article
- A Novel Missense Variant of the ABCD1 Gene in X-Linked Adrenoleukodystrophy in Chinese Family.Molecular genetics & genomic medicine · 2025Article
- The Role of Deubiquitinating Enzymes in Primary Bone Cancer.Molecular biotechnology · 2025Review
- USP37 prevents unscheduled replisome unloading through MCM complex deubiquitination.Nature communications · 2025Article
- An integrative pan-cancer analysis of USP37 and functional validation in pancreatic cancer.Frontiers in cell and developmental biology · 2025Article
- COL12A1 Promotes Osteosarcoma Progression via the FAK/PI3K/AKT/mTOR Pathway.Current molecular medicine · 2025Article
- The future of cancer treatment: combining radiotherapy with immunotherapy.Frontiers in molecular biosciences · 2024Review
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Authors and funding
21 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOsteosarcoma is a type of bone cancer that predominantly affects young individuals, including children and adolescents. The disease progresses through heterogeneous genetic alterations, and patients often develop pulmonary metastases even after the primary tumors have been surgically removed. Ubiquitin-specific peptidases (USPs) regulate several critical cellular processes, such as cell cycle progression, transcriptional activation, and signal transduction. Various studies have revealed the significance of USP37 in the regulation of replication stress and oncogenesis.
methodsIn this study, the Cancer Genome Atlas (TCGA) database was analyzed to investigate USP37 expression. RNA sequencing was utilized to assess the impact of USP37 overexpression and depletion on gene expression in osteosarcoma cells. Various molecular assays, including colony formation, immunofluorescence, immunoprecipitation, and DNA replication restart, were employed to examine the physical interaction between USP37 and PCNA, as well as its physiological effects in osteosarcoma cells. Additionally, molecular docking studies were conducted to gain insight into the nature of the interaction between USP37 and PCNA. Furthermore, immunohistochemistry was performed on archived tissue blocks from osteosarcoma patients to establish a correlation between USP37 and PCNA expression.
resultsAnalysis of the TCGA database revealed that increased expression of USP37 was linked to decreased progression-free survival (PFS) in osteosarcoma patients. Next-generation sequencing analysis of osteosarcoma cells demonstrated that overexpression or knockdown of USP37 led to the expression of different sets of genes. USP37 overexpression provided a survival advantage, while its depletion heightened sensitivity to replication stress in osteosarcoma cells. USP37 was found to physically interact with PCNA, and molecular docking studies indicated that the interaction occurs through unique residues. In response to genotoxic stress, cells that overexpressed USP37 resolved DNA damage foci more quickly than control cells or cells in which USP37 was depleted. The expression of USP37 varied in archived osteosarcoma tissues, with intermediate expression seen in 52% of cases in the cohort examined.
conclusionThe results of this investigation propose that USP37 plays a vital role in promoting replication stress tolerance in osteosarcoma cells. The interaction between USP37 and PCNA is involved in the regulation of replication stress, and disrupting it could potentially trigger synthetic lethality in osteosarcoma. This study has expanded our knowledge of the mechanism through which USP37 regulates replication stress, and its potential as a therapeutic target in osteosarcoma merits additional exploration.
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