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

摘要: Gliomas are aggressive primary brain tumors with high infiltrative potential. The expression of Angiotensin II (Ang II) receptors has been associated poor prognosis in human astrocytomas, the most common type glioma. In this study, we investigated role glioma malignancy through transcriptional profiling and network analysis cultured C6 rat cells exposed to Ang inhibitors its membrane receptor subtypes. were treated specific antagonists AT1 AT2 receptors. Total RNA was isolated after three six hours treatment analyzed by oligonucleotide microarray technology. Gene data evaluated modeling identify how differentially expressed (DE) genes connected each other. Moreover, other co-expressing DE considered these analyses order support identification enriched functions pathways. A hub-based showed that nodes II-related networks exert cell proliferation, migration invasion, key aspects for progression. subsequent functional enrichment central highlighted their participation signaling pathways frequently deregulated gliomas such as ErbB, MAPK p53. Noteworthy, either or inhibitions able down-regulate different sets hub involved protumoral functions, suggesting both could be therapeutic targets intervention Taken together, our results point out multiple actions pathogenesis reveal regulation relevant This study is first one provide systems-level molecular better understanding effects proliferative behavior gliomas.