Analysis of SOX2-Regulated Transcriptome in Glioma Stem Cells

PLoS One. 2016 Sep 26;11(9):e0163155. doi: 10.1371/journal.pone.0163155. eCollection 2016.


Introduction: Glioblastoma is the most malignant brain tumor in adults and is associated with poor survival despite multimodal treatments. Glioma stem-like cells (GSCs) are cells functionally defined by their self-renewal potential and the ability to reconstitute the original tumor upon orthotopic implantation. They have been postulated to be the culprit of glioma chemo- and radio-resistance ultimately leading to relapse. Understanding the molecular circuits governing the GSC compartment is essential. SOX2, a critical transcription regulator of embryonic and neural stem cell function, is deregulated in GSCs however; the precise molecular pathways regulated by this gene in GSCs remain poorly understood.

Results: We performed a genome-wide analysis of SOX2-regulated transcripts in GSCs, using a microarray. We identified a total of 2048 differentially expressed coding transcripts and 261 non-coding transcripts. Cell adhesion and cell-cell signaling are among the most enriched terms using Gene Ontology (GO) classification. The pathways altered after SOX2 down-modulation includes multiple cellular processes such as amino-acid metabolism and intercellular signaling cascades. We also defined and classified the set of non-coding transcripts differentially expressed regulated by SOX2 in GSCs, and validated two of them.

Conclusions: We present a comprehensive analysis of the transcriptome controlled by SOX2 in GSCs, gaining insights in the understanding of the potential roles of SOX2 in glioblastoma.

Grants and funding

This work was supported by the European Union (Marie Curie IRG270459 to MMA), the Instituto de Salud Carlos III y los Fondos Feder Europeos (PI13/125 to MMA), the Spanish Ministry of Economy and competitiveness (IEDI-2015-00638 to MMA), The L`OREAL-Unesco Foundation (to MMA), The Department of Health of the Government of Navarra 22/2015 (to MMA), The Basque Foundation for Health Research (BIOEF, BIO13/CI/005) and Fundación Caja Navarra (Convocatoria de Ayudas 2015 to MMA). AMAR is supported by a fellowship from the Friends of the University of Navarra Foundation.