Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma.
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 those in normal brain tissues, suggesting that a number of miRNAs play critical roles in the pathogenesis o...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC3400583?pdf=render |
| _version_ | 1818180317787193344 |
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| author | Jingchun Sun Xue Gong Benjamin Purow Zhongming Zhao |
| author_facet | Jingchun Sun Xue Gong Benjamin Purow Zhongming Zhao |
| author_sort | Jingchun Sun |
| collection | DOAJ |
| description | 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 those 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. To address this issue, in this study, we systematically explored the main regulation format (feed-forward loops, FFLs) consisting of miRNAs, transcription factors (TFs) and their impacting GBM-related genes, and developed a computational approach to construct a miRNA-TF regulatory network. First, we compiled GBM-related miRNAs, GBM-related genes, and known human TFs. We then identified 1,128 3-node FFLs and 805 4-node FFLs with statistical significance. By merging these FFLs together, we constructed a comprehensive GBM-specific miRNA-TF mediated regulatory network. Then, from the network, we extracted a composite GBM-specific regulatory network. To illustrate the GBM-specific regulatory network is promising for identification of critical miRNA components, we specifically examined a Notch signaling pathway subnetwork. Our follow up topological and functional analyses of the subnetwork 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 results that are supported by previous studies. In this study, we have developed a computational framework to construct a miRNA-TF regulatory network and generated the first miRNA-TF regulatory network for GBM, providing a valuable resource for further understanding the complex regulatory mechanisms in GBM. The observation of critical miRNAs in the Notch signaling pathway, with partial verification from previous studies, demonstrates that our network-based approach is promising for the identification of new and important miRNAs in GBM and, potentially, other cancers. |
| first_indexed | 2024-12-11T21:17:51Z |
| format | Article |
| id | doaj.art-447ef27393004573a9d09dc95a8b76dd |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-11T21:17:51Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-447ef27393004573a9d09dc95a8b76dd2022-12-22T00:50:32ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582012-01-0187e100248810.1371/journal.pcbi.1002488Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma.Jingchun SunXue GongBenjamin PurowZhongming ZhaoGlioblastoma 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 those 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. To address this issue, in this study, we systematically explored the main regulation format (feed-forward loops, FFLs) consisting of miRNAs, transcription factors (TFs) and their impacting GBM-related genes, and developed a computational approach to construct a miRNA-TF regulatory network. First, we compiled GBM-related miRNAs, GBM-related genes, and known human TFs. We then identified 1,128 3-node FFLs and 805 4-node FFLs with statistical significance. By merging these FFLs together, we constructed a comprehensive GBM-specific miRNA-TF mediated regulatory network. Then, from the network, we extracted a composite GBM-specific regulatory network. To illustrate the GBM-specific regulatory network is promising for identification of critical miRNA components, we specifically examined a Notch signaling pathway subnetwork. Our follow up topological and functional analyses of the subnetwork 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 results that are supported by previous studies. In this study, we have developed a computational framework to construct a miRNA-TF regulatory network and generated the first miRNA-TF regulatory network for GBM, providing a valuable resource for further understanding the complex regulatory mechanisms in GBM. The observation of critical miRNAs in the Notch signaling pathway, with partial verification from previous studies, demonstrates that our network-based approach is promising for the identification of new and important miRNAs in GBM and, potentially, other cancers.http://europepmc.org/articles/PMC3400583?pdf=render |
| spellingShingle | Jingchun Sun Xue Gong Benjamin Purow Zhongming Zhao Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma. PLoS Computational Biology |
| title | Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma. |
| title_full | Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma. |
| title_fullStr | Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma. |
| title_full_unstemmed | Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma. |
| title_short | Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma. |
| title_sort | uncovering microrna and transcription factor mediated regulatory networks in glioblastoma |
| url | http://europepmc.org/articles/PMC3400583?pdf=render |
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