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Uncovering differential gene expression between mtRNA-positive and -negative osteosarcoma cells: implications beyond
Xiaoyuan Meng1, Zhongcheng Han2, Wuerkan Yeerken1
1Department of Orthopedics, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
Background:
Long-term clinical outcomes for patients with osteosarcoma have shown little improvement over the past few decades. Identifying novel molecular targets to inhibit osteosarcoma cell growth remains an urgent challenge.
Methods:
Explore the function of mtRNA in the occurrence and development of osteosarcoma utilizing bioinformatics analysis of the Gene Expression Omnibus (GEO) microarray dataset. The Network Analyst tool was used to analyze GSE73120. Differentially expressed genes (DEGs) were identified using GEO2R and analyzed using NetworkAnalyst. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using Metascape and WebGestalt. A protein-protein interaction (PPI) network was constructed through the STRING database and visualized with Cytoscape. The MCODE algorithm was used to identify key modules, and CytoHubba was applied to determine hub genes. Validation of hub genes was conducted using the GEPIA database.
Results:
A total of 104 DEGs were identified, including 89 upregulated and 15 downregulated genes. GO and KEGG analyses revealed that these DEGs were enriched in pathways related to connective tissue development, collagen trimer, and extracellular matrix structural components. The PPI network analysis identified seven hub genes. Among them, COL1A1, PDGFRB, and SPARC were confirmed as sarcoma-related genes using the GEPIA database.
Conclusion:
Our findings suggest that COL1A1, PDGFRB, and SPARC may be involved in mtRNA-driven tumorigenesis and could serve as promising therapeutic targets for osteosarcoma.
Insights
This study identifies key genes (COL1A1, PDGFRB, SPARC) involved in osteosarcoma development, offering potential new therapeutic targets. These findings highlight the role of mitochondrial RNA (mtRNA) in driving sarcoma growth.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Osteosarcoma patient outcomes have seen minimal improvement.
- Novel molecular targets are crucial for inhibiting osteosarcoma cell growth.
Purpose of the Study:
- To explore the role of mitochondrial RNA (mtRNA) in osteosarcoma development using bioinformatics.
- To identify potential therapeutic targets for osteosarcoma.
Main Methods:
- Analysis of Gene Expression Omnibus (GEO) microarray dataset (GSE73120) using GEO2R and NetworkAnalyst.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.
- Protein-protein interaction (PPI) network construction and hub gene identification using STRING, Cytoscape, MCODE, and CytoHubba.
- Validation of hub genes using the GEPIA database.
Main Results:
- Identified 104 differentially expressed genes (DEGs) (89 upregulated, 15 downregulated).
- Enrichment analysis revealed DEGs involved in connective tissue development, collagen trimer, and extracellular matrix.
- Seven hub genes were identified, with COL1A1, PDGFRB, and SPARC confirmed as sarcoma-related.
Conclusions:
- COL1A1, PDGFRB, and SPARC are implicated in mtRNA-driven osteosarcoma tumorigenesis.
- These genes represent promising therapeutic targets for osteosarcoma treatment.
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