Inference of Low and High-Grade Glioma Gene Regulatory Networks Delineates the Role of Rnd3 in Establishing Multiple Hallmarks of Cancer


Gliomas are aggressive brain tumours that are invasive, heterogeneous, refractory to treatment and show poor survival rates. Surgical resection and chemotherapy can increase patient survival but ultimately the disease is fatal. Multiple grades of glioma exist, with lower grades associated to better prognosis. While the majority of high-grade gliomas occur de novo, it is common that low-grade gliomas progress to the more aggressive form known as glioblastoma. In this article, we have shown that by combining advanced network biology approaches with the right experimental models, we are able to reveal novel regulatory circuits controlling multiple hallmarks of glioma. Through analysis of multiple network models representing protein-protein interaction or gene co-expression data we have revealed a switch in the role of regulatory Rho GTPases between low and high-grade gliomas. Amongst these, we show that RND3 is up-regulated in glioblastomas and is a key regulator of tumour proliferation, migration and invasion. We confirm that expression and genomic copy number of RND3 are predictive of clinical outcome, suggesting that changes in the activity of this particular Rho GTPase could be an early event associated to transformation and tumour expansion.


Vyšlo v časopise: Inference of Low and High-Grade Glioma Gene Regulatory Networks Delineates the Role of Rnd3 in Establishing Multiple Hallmarks of Cancer. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005325
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1005325

Souhrn

Gliomas are aggressive brain tumours that are invasive, heterogeneous, refractory to treatment and show poor survival rates. Surgical resection and chemotherapy can increase patient survival but ultimately the disease is fatal. Multiple grades of glioma exist, with lower grades associated to better prognosis. While the majority of high-grade gliomas occur de novo, it is common that low-grade gliomas progress to the more aggressive form known as glioblastoma. In this article, we have shown that by combining advanced network biology approaches with the right experimental models, we are able to reveal novel regulatory circuits controlling multiple hallmarks of glioma. Through analysis of multiple network models representing protein-protein interaction or gene co-expression data we have revealed a switch in the role of regulatory Rho GTPases between low and high-grade gliomas. Amongst these, we show that RND3 is up-regulated in glioblastomas and is a key regulator of tumour proliferation, migration and invasion. We confirm that expression and genomic copy number of RND3 are predictive of clinical outcome, suggesting that changes in the activity of this particular Rho GTPase could be an early event associated to transformation and tumour expansion.


Zdroje

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