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Identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines

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...

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Autores principales: Yang, Xiao-rong, Xiong, Yan, Duan, Hong, Gong, Ren-rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558632/
https://www.ncbi.nlm.nih.gov/pubmed/26337976
http://dx.doi.org/10.1186/s13018-015-0275-8
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author Yang, Xiao-rong
Xiong, Yan
Duan, Hong
Gong, Ren-rong
author_facet Yang, Xiao-rong
Xiong, Yan
Duan, Hong
Gong, Ren-rong
author_sort Yang, Xiao-rong
collection PubMed
description 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.
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spelling pubmed-45586322015-09-04 Identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines Yang, Xiao-rong Xiong, Yan Duan, Hong Gong, Ren-rong J Orthop Surg Res Research Article 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. BioMed Central 2015-09-04 /pmc/articles/PMC4558632/ /pubmed/26337976 http://dx.doi.org/10.1186/s13018-015-0275-8 Text en © Yang et al. 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Yang, Xiao-rong
Xiong, Yan
Duan, Hong
Gong, Ren-rong
Identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines
title Identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines
title_full Identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines
title_fullStr Identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines
title_full_unstemmed Identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines
title_short Identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines
title_sort identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558632/
https://www.ncbi.nlm.nih.gov/pubmed/26337976
http://dx.doi.org/10.1186/s13018-015-0275-8
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