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Functional genomics analyses of RNA-binding proteins reveal the splicing regulator SNRPB as an oncogenic candidate in glioblastoma
BACKGROUND: Glioblastoma (GBM) is the most common and aggressive type of brain tumor. Currently, GBM has an extremely poor outcome and there is no effective treatment. In this context, genomic and transcriptomic analyses have become important tools to identify new avenues for therapies. RNA-binding...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901439/ https://www.ncbi.nlm.nih.gov/pubmed/27287018 http://dx.doi.org/10.1186/s13059-016-0990-4 |
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author | Correa, Bruna R. de Araujo, Patricia Rosa Qiao, Mei Burns, Suzanne C. Chen, Chen Schlegel, Richard Agarwal, Seema Galante, Pedro A. F. Penalva, Luiz O. F. |
author_facet | Correa, Bruna R. de Araujo, Patricia Rosa Qiao, Mei Burns, Suzanne C. Chen, Chen Schlegel, Richard Agarwal, Seema Galante, Pedro A. F. Penalva, Luiz O. F. |
author_sort | Correa, Bruna R. |
collection | PubMed |
description | BACKGROUND: Glioblastoma (GBM) is the most common and aggressive type of brain tumor. Currently, GBM has an extremely poor outcome and there is no effective treatment. In this context, genomic and transcriptomic analyses have become important tools to identify new avenues for therapies. RNA-binding proteins (RBPs) are master regulators of co- and post-transcriptional events; however, their role in GBM remains poorly understood. To further our knowledge of novel regulatory pathways that could contribute to gliomagenesis, we have conducted a systematic study of RBPs in GBM. RESULTS: By measuring expression levels of 1542 human RBPs in GBM samples and glioma stem cell samples, we identified 58 consistently upregulated RBPs. Survival analysis revealed that increased expression of 21 RBPs was also associated with a poor prognosis. To assess the functional impact of those RBPs, we modulated their expression in GBM cell lines and performed viability, proliferation, and apoptosis assays. Combined results revealed a prominent oncogenic candidate, SNRPB, which encodes core spliceosome machinery components. To reveal the impact of SNRPB on splicing and gene expression, we performed its knockdown in a GBM cell line followed by RNA sequencing. We found that the affected genes were involved in RNA processing, DNA repair, and chromatin remodeling. Additionally, genes and pathways already associated with gliomagenesis, as well as a set of general cancer genes, also presented with splicing and expression alterations. CONCLUSIONS: Our study provides new insights into how RBPs, and specifically SNRPB, regulate gene expression and directly impact GBM development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-0990-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4901439 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-49014392016-06-11 Functional genomics analyses of RNA-binding proteins reveal the splicing regulator SNRPB as an oncogenic candidate in glioblastoma Correa, Bruna R. de Araujo, Patricia Rosa Qiao, Mei Burns, Suzanne C. Chen, Chen Schlegel, Richard Agarwal, Seema Galante, Pedro A. F. Penalva, Luiz O. F. Genome Biol Research BACKGROUND: Glioblastoma (GBM) is the most common and aggressive type of brain tumor. Currently, GBM has an extremely poor outcome and there is no effective treatment. In this context, genomic and transcriptomic analyses have become important tools to identify new avenues for therapies. RNA-binding proteins (RBPs) are master regulators of co- and post-transcriptional events; however, their role in GBM remains poorly understood. To further our knowledge of novel regulatory pathways that could contribute to gliomagenesis, we have conducted a systematic study of RBPs in GBM. RESULTS: By measuring expression levels of 1542 human RBPs in GBM samples and glioma stem cell samples, we identified 58 consistently upregulated RBPs. Survival analysis revealed that increased expression of 21 RBPs was also associated with a poor prognosis. To assess the functional impact of those RBPs, we modulated their expression in GBM cell lines and performed viability, proliferation, and apoptosis assays. Combined results revealed a prominent oncogenic candidate, SNRPB, which encodes core spliceosome machinery components. To reveal the impact of SNRPB on splicing and gene expression, we performed its knockdown in a GBM cell line followed by RNA sequencing. We found that the affected genes were involved in RNA processing, DNA repair, and chromatin remodeling. Additionally, genes and pathways already associated with gliomagenesis, as well as a set of general cancer genes, also presented with splicing and expression alterations. CONCLUSIONS: Our study provides new insights into how RBPs, and specifically SNRPB, regulate gene expression and directly impact GBM development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-0990-4) contains supplementary material, which is available to authorized users. BioMed Central 2016-06-10 /pmc/articles/PMC4901439/ /pubmed/27287018 http://dx.doi.org/10.1186/s13059-016-0990-4 Text en © The Author(s). 2016 Open AccessThis 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 Correa, Bruna R. de Araujo, Patricia Rosa Qiao, Mei Burns, Suzanne C. Chen, Chen Schlegel, Richard Agarwal, Seema Galante, Pedro A. F. Penalva, Luiz O. F. Functional genomics analyses of RNA-binding proteins reveal the splicing regulator SNRPB as an oncogenic candidate in glioblastoma |
title | Functional genomics analyses of RNA-binding proteins reveal the splicing regulator SNRPB as an oncogenic candidate in glioblastoma |
title_full | Functional genomics analyses of RNA-binding proteins reveal the splicing regulator SNRPB as an oncogenic candidate in glioblastoma |
title_fullStr | Functional genomics analyses of RNA-binding proteins reveal the splicing regulator SNRPB as an oncogenic candidate in glioblastoma |
title_full_unstemmed | Functional genomics analyses of RNA-binding proteins reveal the splicing regulator SNRPB as an oncogenic candidate in glioblastoma |
title_short | Functional genomics analyses of RNA-binding proteins reveal the splicing regulator SNRPB as an oncogenic candidate in glioblastoma |
title_sort | functional genomics analyses of rna-binding proteins reveal the splicing regulator snrpb as an oncogenic candidate in glioblastoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901439/ https://www.ncbi.nlm.nih.gov/pubmed/27287018 http://dx.doi.org/10.1186/s13059-016-0990-4 |
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