Analysis of SOX2-regulated transcriptome in glioma stem cells

Abstract

Introduction

Glioblastoma is the most malignant brain tumor in adults and is associated with poor sur- vival 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 govern- ing 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 path- ways 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 inter- cellular 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.