NDLI: Hierarchical control of coherent gene clusters defines the molecular mechanisms of glioblastoma.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Tsigelny, Igor F. Kouznetsova, Valentina L. Jiang, Pengfei Pingle, Sandeep C. Kesari, Santosh
Description	Country affiliation: United States Author Affiliation: Tsigelny IF ( Department of Neurosciences, University of California San Diego, 9500 Gilman Dr., MSC 0752, La Jolla, CA 92093-0752, USA. itsigeln@ucsd.edu.)
Abstract	Glioblastoma is a highly-aggressive and rapidly-lethal tumor characterized by resistance to therapy. Although data on multiple genes, proteins, and pathways are available, the key challenge is deciphering this information and identifying central molecular targets. Therapeutically targeting individual molecules is often unsuccessful due to the presence of compensatory and redundant pathways, and crosstalk. A systems biology approach that involves a hierarchical gene group networks analysis can delineate the coherent functions of different disease mediators. Here, we report an integrative networks-based analysis to identify a system of coherent gene modules in primary and secondary glioblastoma. Our study revealed a hierarchical transcriptional control of genes in these modules. We elucidated those modules responsible for conversion of the glioma-associated microglia/macrophages into glioma-supportive, immunosuppressive cells. Further, we identified clusters comprising mediators of angiogenesis, proliferation, and cell death for both primary and secondary glioblastomas. Data obtained for these clusters point to a possible role of transcription regulators that function as the gene modules mediators in glioblastoma pathogenesis. We elucidated a set of possible transcription regulators that can be targeted to affect the selected gene clusters at specific levels for glioblastoma. Our innovative approach to construct informative disease models may hold the key to successful management of complex diseases including glioblastoma and other cancers.
File Format	HTM / HTML
ISSN	1742206X
Issue Number	4
Volume Number	11
e-ISSN	17422051
Journal	Molecular BioSystems
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2015-04-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Discipline Molecular Biology Discipline Biochemistry Brain Neoplasms Genetics Gene Expression Regulation, Neoplastic Glioblastoma Multigene Family Brain Metabolism Cell Death Cell Proliferation Gene Expression Profiling Humans Neovascularization, Pathologic Oligonucleotide Array Sequence Analysis Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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