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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Transcriptional Network Analysis Reveals that AT1 and AT2 Angiotensin II Receptors Are Both Involved in the Regulation of Genes Essential for Glioma Progression

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Author(s):
Azevedo, Hatylas [1] ; Fujita, Andre [2] ; Bando, Silvia Yumi [1] ; Iamashita, Priscila [1] ; Moreira-Filho, Carlos Alberto [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Fac Med, Dept Pediat, Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Comp Sci, Inst Matemat & Estat, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: PLoS One; v. 9, n. 11 NOV 3 2014.
Web of Science Citations: 9
Abstract

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. (AU)

FAPESP's process: 11/07762-8 - Granger causality for sets of time series: development of methodologies to model selection and extensions in the frequency domain with applications to molecular biology and neuroscience
Grantee:André Fujita
Support type: Regular Research Grants
FAPESP's process: 05/56446-0 - High resolutions structural MRI and receptor imaging studies in refractory temporal lobe epilepsy: in vivo and ex vivo analyses
Grantee:Edson Amaro Junior
Support type: Inter-institutional Cooperation in Support of Brain Research (CINAPCE) - Thematic Grants
FAPESP's process: 11/50761-2 - Models and methods of e-Science for life and agricultural sciences
Grantee:Roberto Marcondes Cesar Junior
Support type: Research Projects - Thematic Grants
FAPESP's process: 09/53443-1 - Neuroimmunology, functional genomics and neuroimaging: an integrated approach for studying physiopathology and treatment in refractory epilepsy
Grantee:Carlos Alberto Moreira Filho
Support type: Research Projects - Thematic Grants