Analysis of SOX2-Regulated Transcriptome in Glioma Stem Cells

作者：de la Rocha Arlet M Acanda; Lopez Bertoni Hernando; Guruceaga Elizabeth; Gonzalez Huarriz Marisol; Martinez Velez Naiara; Xipell Enric; Fueyo Juan; Gomez Manzano Candelaria; Alonso Marta M^*

来源：PLos One, 2016, 11(9): e0163155.

DOI：10.1371/journal.pone.0163155

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.

• 出版日期2016-9-26