Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in humans. Recent studies revealed that patterns of microRNA (miRNA) expression in GBM tissue samples are different from that in normal brain tissues, suggesting that a number of miRNAs play critical roles in the pathogenesis of GBM. However, little is yet known about which miRNAs play central roles in the pathology of GBM and their regulatory mechanisms of action. In this study, we systematically explored the combinatory regulation of miRNAs and transcription factors (TFs) impacting GBM genes. We compiled GBM-related miRNAs, genes, and TFs and then identified 1,128 3-node feed-forward loops (FFLs) and 805 4-node FFLs with statistical significance. These FFLs were converged to construct a comprehensive GBM-specific miRNA-TF mediated regulatory network and, from which, an essential GBM-specific regulatory network. To further identify critical miRNA components in the GBM regulatory network, we specifically extracted a subnetwork for Notch signaling pathway. Our follow up network and functional association analyses revealed that six miRNAs (miR-124, miR-137, miR-219-5p, miR-34a, miR-9, and miR-92b) might play important roles in GBM, including some supported by previous studies. This study has generated the first comprehensive miRNA-TF regulatory network for GBM, providing a valuable resource for further understanding the complex regulatory mechanisms in GBM. Our findings of important miRNAs in the Notch signaling pathway, with partial verification by previous studies, demonstrates that our network-based approach is promising for identifying new and important miRNAs in GBM and, potentially, other cancers.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4948. doi:1538-7445.AM2012-4948