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Establishing an osteosarcoma associated protein-protein interaction network to explore the pathogenesis of osteosarcoma.

ABSTRACT: BACKGROUND: The aim of this study was to establish an osteosarcoma (OS) associated protein-protein interaction network and explore the pathogenesis of osteosarcoma. METHODS: The gene expression profile GSE9508 was downloaded from the Gene Expression Omnibus database, including five samples of non-malignant bone (the control), seven samples for non-metastatic patients (six of which were analyzed in duplicate), and 11 samples for metastatic patients (10 of which were analyzed in duplicate). Differentially expressed genes (DEGs) between osteosarcoma and control samples were identified by packages in R with the threshold of |logFC (fold change)|?>?1 and false discovery rate?

SUBMITTER: Deng BY

PROVIDER: S-EPMC3878683 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Establishing an osteosarcoma associated protein-protein interaction network to explore the pathogenesis of osteosarcoma.

Deng Bi-Yong BY Hua Ying-Qi YQ Cai Zheng-Dong ZD

European journal of medical research 20131214

<h4>Background</h4>The aim of this study was to establish an osteosarcoma (OS) associated protein-protein interaction network and explore the pathogenesis of osteosarcoma.<h4>Methods</h4>The gene expression profile GSE9508 was downloaded from the Gene Expression Omnibus database, including five samples of non-malignant bone (the control), seven samples for non-metastatic patients (six of which were analyzed in duplicate), and 11 samples for metastatic patients (10 of which were analyzed in dupli ...[more]

PMID: 24330838

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Project description: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.

Dataset Information

Establishing an osteosarcoma associated protein-protein interaction network to explore the pathogenesis of osteosarcoma.

Publications

Establishing an osteosarcoma associated protein-protein interaction network to explore the pathogenesis of osteosarcoma.

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