Transcriptional network analysis reveals that AT1 and AT2 angiotensin II receptors are both involved in the regulation of genes essential for glioma progression.

Gliomas are aggressive primary brain tumors with high infiltrative potential. The expression of Angiotensin II (Ang II) receptors has been associated with poor prognosis in human astrocytomas, the most common type of glioma. In this study, we investigated the role of Angiotensin II in glioma maligna...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hátylas Azevedo, André Fujita, Silvia Yumi Bando, Priscila Iamashita, Carlos Alberto Moreira-Filho
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7a0616af5f214e54b774f6d9dbb100a5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7a0616af5f214e54b774f6d9dbb100a5
record_format	dspace
spelling	oai:doaj.org-article:7a0616af5f214e54b774f6d9dbb100a52021-11-25T05:54:46ZTranscriptional network analysis reveals that AT1 and AT2 angiotensin II receptors are both involved in the regulation of genes essential for glioma progression.1932-620310.1371/journal.pone.0110934https://doaj.org/article/7a0616af5f214e54b774f6d9dbb100a52014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0110934https://doaj.org/toc/1932-6203Gliomas are aggressive primary brain tumors with high infiltrative potential. The expression of Angiotensin II (Ang II) receptors has been associated with poor prognosis in human astrocytomas, the most common type of glioma. In this study, we investigated the role of Angiotensin II in glioma malignancy through transcriptional profiling and network analysis of cultured C6 rat glioma cells exposed to Ang II and to inhibitors of its membrane receptor subtypes. C6 cells were treated with Ang II and specific antagonists of AT1 and AT2 receptors. Total RNA was isolated after three and six hours of Ang II treatment and analyzed by oligonucleotide microarray technology. Gene expression data was evaluated through transcriptional network modeling to identify how differentially expressed (DE) genes are connected to each other. Moreover, other genes co-expressing with the DE genes were considered in these analyses in order to support the identification of enriched functions and pathways. A hub-based network analysis showed that the most connected nodes in Ang II-related networks exert functions associated with cell proliferation, migration and invasion, key aspects for glioma progression. The subsequent functional enrichment analysis of these central genes highlighted their participation in signaling pathways that are frequently deregulated in gliomas such as ErbB, MAPK and p53. Noteworthy, either AT1 or AT2 inhibitions were able to down-regulate different sets of hub genes involved in protumoral functions, suggesting that both Ang II receptors could be therapeutic targets for intervention in glioma. Taken together, our results point out multiple actions of Ang II in glioma pathogenesis and reveal the participation of both Ang II receptors in the regulation of genes relevant for glioma progression. This study is the first one to provide systems-level molecular data for better understanding the protumoral effects of Ang II in the proliferative and infiltrative behavior of gliomas.Hátylas AzevedoAndré FujitaSilvia Yumi BandoPriscila IamashitaCarlos Alberto Moreira-FilhoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 11, p e110934 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hátylas Azevedo André Fujita Silvia Yumi Bando Priscila Iamashita Carlos Alberto Moreira-Filho Transcriptional network analysis reveals that AT1 and AT2 angiotensin II receptors are both involved in the regulation of genes essential for glioma progression.
description	Gliomas are aggressive primary brain tumors with high infiltrative potential. The expression of Angiotensin II (Ang II) receptors has been associated with poor prognosis in human astrocytomas, the most common type of glioma. In this study, we investigated the role of Angiotensin II in glioma malignancy through transcriptional profiling and network analysis of cultured C6 rat glioma cells exposed to Ang II and to inhibitors of its membrane receptor subtypes. C6 cells were treated with Ang II and specific antagonists of AT1 and AT2 receptors. Total RNA was isolated after three and six hours of Ang II treatment and analyzed by oligonucleotide microarray technology. Gene expression data was evaluated through transcriptional network modeling to identify how differentially expressed (DE) genes are connected to each other. Moreover, other genes co-expressing with the DE genes were considered in these analyses in order to support the identification of enriched functions and pathways. A hub-based network analysis showed that the most connected nodes in Ang II-related networks exert functions associated with cell proliferation, migration and invasion, key aspects for glioma progression. The subsequent functional enrichment analysis of these central genes highlighted their participation in signaling pathways that are frequently deregulated in gliomas such as ErbB, MAPK and p53. Noteworthy, either AT1 or AT2 inhibitions were able to down-regulate different sets of hub genes involved in protumoral functions, suggesting that both Ang II receptors could be therapeutic targets for intervention in glioma. Taken together, our results point out multiple actions of Ang II in glioma pathogenesis and reveal the participation of both Ang II receptors in the regulation of genes relevant for glioma progression. This study is the first one to provide systems-level molecular data for better understanding the protumoral effects of Ang II in the proliferative and infiltrative behavior of gliomas.
format	article
author	Hátylas Azevedo André Fujita Silvia Yumi Bando Priscila Iamashita Carlos Alberto Moreira-Filho
author_facet	Hátylas Azevedo André Fujita Silvia Yumi Bando Priscila Iamashita Carlos Alberto Moreira-Filho
author_sort	Hátylas Azevedo
title	Transcriptional network analysis reveals that AT1 and AT2 angiotensin II receptors are both involved in the regulation of genes essential for glioma progression.
title_short	Transcriptional network analysis reveals that AT1 and AT2 angiotensin II receptors are both involved in the regulation of genes essential for glioma progression.
title_full	Transcriptional network analysis reveals that AT1 and AT2 angiotensin II receptors are both involved in the regulation of genes essential for glioma progression.
title_fullStr	Transcriptional network analysis reveals that AT1 and AT2 angiotensin II receptors are both involved in the regulation of genes essential for glioma progression.
title_full_unstemmed	Transcriptional network analysis reveals that AT1 and AT2 angiotensin II receptors are both involved in the regulation of genes essential for glioma progression.
title_sort	transcriptional network analysis reveals that at1 and at2 angiotensin ii receptors are both involved in the regulation of genes essential for glioma progression.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/7a0616af5f214e54b774f6d9dbb100a5
work_keys_str_mv	AT hatylasazevedo transcriptionalnetworkanalysisrevealsthatat1andat2angiotensiniireceptorsarebothinvolvedintheregulationofgenesessentialforgliomaprogression AT andrefujita transcriptionalnetworkanalysisrevealsthatat1andat2angiotensiniireceptorsarebothinvolvedintheregulationofgenesessentialforgliomaprogression AT silviayumibando transcriptionalnetworkanalysisrevealsthatat1andat2angiotensiniireceptorsarebothinvolvedintheregulationofgenesessentialforgliomaprogression AT priscilaiamashita transcriptionalnetworkanalysisrevealsthatat1andat2angiotensiniireceptorsarebothinvolvedintheregulationofgenesessentialforgliomaprogression AT carlosalbertomoreirafilho transcriptionalnetworkanalysisrevealsthatat1andat2angiotensiniireceptorsarebothinvolvedintheregulationofgenesessentialforgliomaprogression
_version_	1718414409813983232

Transcriptional network analysis reveals that AT1 and AT2 angiotensin II receptors are both involved in the regulation of genes essential for glioma progression.

Ejemplares similares