Differential gene expression analysis by RNA-seq reveals the importance of actin cytoskeletal proteins in erythroleukemia cells
Development of drug resistance limits the effectiveness of anticancer treatments. Understanding the molecular mechanisms triggering this event in tumor cells may lead to improved therapeutic strategies. Here we used RNA-seq to compare the transcriptomes of a murine erythroleukemia cell line (MEL) an...
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PeerJ Inc.
2017-06-01
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| Online Access: | https://peerj.com/articles/3432.pdf |
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| author | Vanessa Fernández-Calleja Pablo Hernández Jorge B. Schvartzman Mario García de Lacoba Dora B. Krimer |
| author_facet | Vanessa Fernández-Calleja Pablo Hernández Jorge B. Schvartzman Mario García de Lacoba Dora B. Krimer |
| author_sort | Vanessa Fernández-Calleja |
| collection | DOAJ |
| description | Development of drug resistance limits the effectiveness of anticancer treatments. Understanding the molecular mechanisms triggering this event in tumor cells may lead to improved therapeutic strategies. Here we used RNA-seq to compare the transcriptomes of a murine erythroleukemia cell line (MEL) and a derived cell line with induced resistance to differentiation (MEL-R). RNA-seq analysis identified a total of 596 genes (Benjamini–Hochberg adjusted p-value < 0.05) that were differentially expressed by more than two-fold, of which 81.5% (486/596) of genes were up-regulated in MEL cells and 110 up-regulated in MEL-R cells. These observations revealed that for some genes the relative expression of mRNA amount in the MEL cell line has decreased as the cells acquired the resistant phenotype. Clustering analysis of a group of genes showing the highest differential expression allowed identification of a sub-group among genes up-regulated in MEL cells. These genes are related to the organization of the actin cytoskeleton network. Moreover, the majority of these genes are preferentially expressed in the hematopoietic lineage and at least three of them, Was (Wiskott Aldrich syndrome), Btk (Bruton’s tyrosine kinase) and Rac2, when mutated in humans, give rise to severe hematopoietic deficiencies. Among the group of genes that were up-regulated in MEL-R cells, 16% of genes code for histone proteins, both canonical and variants. A potential implication of these results on the blockade of differentiation in resistant cells is discussed. |
| first_indexed | 2024-03-09T06:59:35Z |
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| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:59:35Z |
| publishDate | 2017-06-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
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| spelling | doaj.art-e5bdfcc15a7e4ef0a682e358c2a1e8262023-12-03T09:58:02ZengPeerJ Inc.PeerJ2167-83592017-06-015e343210.7717/peerj.3432Differential gene expression analysis by RNA-seq reveals the importance of actin cytoskeletal proteins in erythroleukemia cellsVanessa Fernández-Calleja0Pablo Hernández1Jorge B. Schvartzman2Mario García de Lacoba3Dora B. Krimer4Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas, Spanish National Research Council (CSIC), Madrid, SpainDepartment of Cellular and Molecular Biology, Centro de Investigaciones Biológicas, Spanish National Research Council (CSIC), Madrid, SpainDepartment of Cellular and Molecular Biology, Centro de Investigaciones Biológicas, Spanish National Research Council (CSIC), Madrid, SpainBioinformatics and Biostatistics Service, Centro de Investigaciones Biológicas, Spanish National Research Council (CSIC), Madrid, SpainDepartment of Cellular and Molecular Biology, Centro de Investigaciones Biológicas, Spanish National Research Council (CSIC), Madrid, SpainDevelopment of drug resistance limits the effectiveness of anticancer treatments. Understanding the molecular mechanisms triggering this event in tumor cells may lead to improved therapeutic strategies. Here we used RNA-seq to compare the transcriptomes of a murine erythroleukemia cell line (MEL) and a derived cell line with induced resistance to differentiation (MEL-R). RNA-seq analysis identified a total of 596 genes (Benjamini–Hochberg adjusted p-value < 0.05) that were differentially expressed by more than two-fold, of which 81.5% (486/596) of genes were up-regulated in MEL cells and 110 up-regulated in MEL-R cells. These observations revealed that for some genes the relative expression of mRNA amount in the MEL cell line has decreased as the cells acquired the resistant phenotype. Clustering analysis of a group of genes showing the highest differential expression allowed identification of a sub-group among genes up-regulated in MEL cells. These genes are related to the organization of the actin cytoskeleton network. Moreover, the majority of these genes are preferentially expressed in the hematopoietic lineage and at least three of them, Was (Wiskott Aldrich syndrome), Btk (Bruton’s tyrosine kinase) and Rac2, when mutated in humans, give rise to severe hematopoietic deficiencies. Among the group of genes that were up-regulated in MEL-R cells, 16% of genes code for histone proteins, both canonical and variants. A potential implication of these results on the blockade of differentiation in resistant cells is discussed.https://peerj.com/articles/3432.pdfRNA-seqCell differentiationHMBA-resistantWiskott-Aldrich syndromeBruton’s tyrosine kinaseErytrhroleukemia cells |
| spellingShingle | Vanessa Fernández-Calleja Pablo Hernández Jorge B. Schvartzman Mario García de Lacoba Dora B. Krimer Differential gene expression analysis by RNA-seq reveals the importance of actin cytoskeletal proteins in erythroleukemia cells PeerJ RNA-seq Cell differentiation HMBA-resistant Wiskott-Aldrich syndrome Bruton’s tyrosine kinase Erytrhroleukemia cells |
| title | Differential gene expression analysis by RNA-seq reveals the importance of actin cytoskeletal proteins in erythroleukemia cells |
| title_full | Differential gene expression analysis by RNA-seq reveals the importance of actin cytoskeletal proteins in erythroleukemia cells |
| title_fullStr | Differential gene expression analysis by RNA-seq reveals the importance of actin cytoskeletal proteins in erythroleukemia cells |
| title_full_unstemmed | Differential gene expression analysis by RNA-seq reveals the importance of actin cytoskeletal proteins in erythroleukemia cells |
| title_short | Differential gene expression analysis by RNA-seq reveals the importance of actin cytoskeletal proteins in erythroleukemia cells |
| title_sort | differential gene expression analysis by rna seq reveals the importance of actin cytoskeletal proteins in erythroleukemia cells |
| topic | RNA-seq Cell differentiation HMBA-resistant Wiskott-Aldrich syndrome Bruton’s tyrosine kinase Erytrhroleukemia cells |
| url | https://peerj.com/articles/3432.pdf |
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