Analysis of SOX2-Regulated Transcriptome in Glioma Stem Cells.
BACKGROUND
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.
The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Department of Pediatrics, University Hospital of Navarra, Pamplona, Spain.
Arlet M
AM
Acanda de la Rocha
Hugo W Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, United States of America.|Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
Hernando
H
López-Bertoni
The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Bioinformatics Unit, Center for Applied Medical Research, Pamplona, Spain.
Elizabeth
E
Guruceaga
The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Department of Pediatrics, University Hospital of Navarra, Pamplona, Spain.
Marisol
M
González-Huarriz
The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Department of Pediatrics, University Hospital of Navarra, Pamplona, Spain.
Naiara
N
Martínez-Vélez
The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Department of Pediatrics, University Hospital of Navarra, Pamplona, Spain.
Enric
E
Xipell
Brain Tumor Center, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Juan
J
Fueyo
Brain Tumor Center, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Candelaria
C
Gomez-Manzano
The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Department of Pediatrics, University Hospital of Navarra, Pamplona, Spain.
Marta M
http://orcid.org/0000-0002-7520-7351
MM
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