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Updated: Apr 4, 2026

LINE-1 Methylation Analysis in Mesenchymal Stem Cells Treated with Osteosarcoma-Derived Extracellular Vesicles
Published on: February 1, 2020
Identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines
Xiao-Rong Yang1, Yan Xiong2, Hong Duan3
1Department of Operation Room, West China Hospital, Sichuan University, No 37, Guo Xue Lane, Chengdu, Sichuan, 610041, People's Republic of China. jafsdfdfs@163.com.
Background:
This study aimed to better understand the mechanisms underlying methotrexate (MTX)-resistance in osteosarcoma.
Methods:
The raw transcription microarray data GSE16089 collected from three MTX-sensitive osteosarcoma (Saos-2) cell samples and three MTX-resistant osteosarcoma (Saos-2) cell samples were downloaded from Gene Expression Omnibus. After data processing, the differentially expressed genes (DEGs) were identified. Next, DEGs were submitted to DAVID for functional annotation based on the GO (Gene Ontology) database, as well as pathway enrichment analysis based on the KEGG (Kyoto Encyclopedia of Genes and Genomes) database. Transcription factors (TFs) and tumor-associated genes (TAGs) were identified with reference to TRANSFAC and TAG, and TSGene databases, respectively. The protein-protein interaction (PPI) network of the gene-encoded products was constructed, and the subnetwork with the highest score was also detected using Search Tool for the Retrieval of Interacting Genes and BioNet package.
Results:
A total of 690 up-regulated genes and down-regulated 626 genes were identified. Up-regulated DEGs (including AARS and PARS2) were associated to transfer RNA (tRNA) aminoacylation while down-regulated DEGs (including AURKA, CCNB1, CCNE2, CDK1, and CENPA) were correlated with mitotic cell cycle. Totally, 13 TFs (including HMGB2), 13 oncogenes (including CCNA2 and AURKA), and 19 tumor suppressor genes (TSGs) (including CDKN2C) were identified from the down-regulated DEGs. Ten DEGs, including nine down-regulated genes (such as AURKA, CDK1, CCNE2, and CENPA) and one up-regulated gene (GADD45A), were involved in the highest score subnetwork.
Conclusion:
AARS, AURKA, AURKB, CENPA, CCNB1, CCNE2, and CDK may contribute to MTX resistance via aminoacyl-tRNA biosynthesis pathway, cell cycle pathway, or p53 signaling pathway.
Insights
Methotrexate resistance in osteosarcoma is linked to altered gene expression. Key genes in aminoacyl-tRNA biosynthesis and cell cycle pathways may drive this resistance, offering potential therapeutic targets.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Osteosarcoma is a primary bone cancer with significant treatment challenges.
- Methotrexate (MTX) is a chemotherapy agent used in osteosarcoma treatment.
- Understanding MTX resistance mechanisms is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the molecular mechanisms of methotrexate (MTX) resistance in osteosarcoma.
- To identify differentially expressed genes (DEGs) associated with MTX resistance.
- To explore the functional roles of these DEGs in osteosarcoma progression.
Main Methods:
- Microarray data (GSE16089) from MTX-sensitive and resistant osteosarcoma cells were analyzed.
- Differentially expressed genes (DEGs) were identified and functionally annotated using GO and KEGG databases.
- Transcription factors (TFs), tumor-associated genes (TAGs), and protein-protein interaction (PPI) networks were constructed.
Main Results:
- 690 up-regulated and 626 down-regulated genes were identified.
- Up-regulated genes were linked to transfer RNA (tRNA) aminoacylation (e.g., AARS, PARS2).
- Down-regulated genes were associated with the mitotic cell cycle (e.g., AURKA, CCNB1, CDK1, CENPA).
Conclusions:
- Genes such as AARS, AURKA, AURKB, CENPA, CCNB1, CCNE2, and CDK1 may contribute to MTX resistance.
- These genes are implicated in aminoacyl-tRNA biosynthesis, cell cycle regulation, and p53 signaling pathways.
- Identifying these genes provides insights into potential therapeutic strategies for overcoming MTX resistance in osteosarcoma.
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