Limits...
Analysis of SOX2-Regulated Transcriptome in Glioma Stem Cells

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

10-Top Bio Functions categories altered following SOX2 inhibition.The categories listed are Physiological System Development and Function, Molecular and cellular Functions and Disease and Disorders, identified using IPA software. Bars represent the number of genes in the specified category, organized by p-value.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5036841&req=5

pone.0163155.g004: 10-Top Bio Functions categories altered following SOX2 inhibition.The categories listed are Physiological System Development and Function, Molecular and cellular Functions and Disease and Disorders, identified using IPA software. Bars represent the number of genes in the specified category, organized by p-value.

Mentions: The IPA analysis also showed the most relevant biological functions and diseases in our data set. The most significant bio-functions altered following SOX2 down-modulation are showed in Table 5. The set of SOX2-associated genes were assigned mainly to the following networks: “cancer”, “organismal injury and abnormalities”, “cellular movement”, “tissue morphology”, “cellular development” and “hematopoiesis”. Interestingly, most of these networks involved very well-known functions of SOX2 such as morphology determination [36], development [37] and cellular proliferation and migration in glioma [13,13]. Fig 4 shows the most relevant selection of bio-function categories: disease and disorders, molecular and cellular functions and physiological system development and function, obtained by using IPA software organized by p-value.


Analysis of SOX2-Regulated Transcriptome in Glioma Stem Cells
10-Top Bio Functions categories altered following SOX2 inhibition.The categories listed are Physiological System Development and Function, Molecular and cellular Functions and Disease and Disorders, identified using IPA software. Bars represent the number of genes in the specified category, organized by p-value.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036841&req=5

pone.0163155.g004: 10-Top Bio Functions categories altered following SOX2 inhibition.The categories listed are Physiological System Development and Function, Molecular and cellular Functions and Disease and Disorders, identified using IPA software. Bars represent the number of genes in the specified category, organized by p-value.
Mentions: The IPA analysis also showed the most relevant biological functions and diseases in our data set. The most significant bio-functions altered following SOX2 down-modulation are showed in Table 5. The set of SOX2-associated genes were assigned mainly to the following networks: “cancer”, “organismal injury and abnormalities”, “cellular movement”, “tissue morphology”, “cellular development” and “hematopoiesis”. Interestingly, most of these networks involved very well-known functions of SOX2 such as morphology determination [36], development [37] and cellular proliferation and migration in glioma [13,13]. Fig 4 shows the most relevant selection of bio-function categories: disease and disorders, molecular and cellular functions and physiological system development and function, obtained by using IPA software organized by p-value.

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus