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.


SOX2 regulated non-coding transcripts.(A) A total of 261 transcripts were found differentially expressed (B > 0), which were distributed in 80 upregulated and 181 downregulated transcripts. (B) Biotype distribution of the differentially expressed transcripts following SOX2 down-modulation in GSC11 cells.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0163155.g005: SOX2 regulated non-coding transcripts.(A) A total of 261 transcripts were found differentially expressed (B > 0), which were distributed in 80 upregulated and 181 downregulated transcripts. (B) Biotype distribution of the differentially expressed transcripts following SOX2 down-modulation in GSC11 cells.

Mentions: Reprogramming transcription factors, including SOX2, have been shown to regulate both coding and non-coding RNAs [38]. LncRNAs are emerging as key regulators of biological processes and disease [39] therefore, seems reasonable to hypothesize that SOX2 will regulate this class of genes as well. The strength of our data-sets allowed us to identify potential non-coding transcripts differentially expressed (B value > 0) regulated by SOX2 in GSCs. After biotype distribution analysis we identify protein coding RNAs (44% for up-regulated and 41% for down-regulated), while the rest were classified as different types of non-coding transcripts. Out of the total number of transcripts differentially expressed we identify 80 upregulated and 181 down-regulated and we classify them as intergenic RNAs, antisense, processed transcripts, transcripts derived from pseudogenes and unassigned transcripts (Fig 5). The transcripts classified as “others” correspond to transcripts derived from miRNAs, rRNAs, sense-overlaping and sense intronic transcripts. The lncRNA annotation was performed with the Bioconductor package ChIPpeakAnno [40] and using Gencode v19 as reference [41]. The gene type corresponding to the gene that overlaps with the lincRNA locus was assigned to each lincRNA. Table 6 shows the top 25 non-coding transcripts regulated by SOX2 in GSCs.


Analysis of SOX2-Regulated Transcriptome in Glioma Stem Cells
SOX2 regulated non-coding transcripts.(A) A total of 261 transcripts were found differentially expressed (B > 0), which were distributed in 80 upregulated and 181 downregulated transcripts. (B) Biotype distribution of the differentially expressed transcripts following SOX2 down-modulation in GSC11 cells.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0163155.g005: SOX2 regulated non-coding transcripts.(A) A total of 261 transcripts were found differentially expressed (B > 0), which were distributed in 80 upregulated and 181 downregulated transcripts. (B) Biotype distribution of the differentially expressed transcripts following SOX2 down-modulation in GSC11 cells.
Mentions: Reprogramming transcription factors, including SOX2, have been shown to regulate both coding and non-coding RNAs [38]. LncRNAs are emerging as key regulators of biological processes and disease [39] therefore, seems reasonable to hypothesize that SOX2 will regulate this class of genes as well. The strength of our data-sets allowed us to identify potential non-coding transcripts differentially expressed (B value > 0) regulated by SOX2 in GSCs. After biotype distribution analysis we identify protein coding RNAs (44% for up-regulated and 41% for down-regulated), while the rest were classified as different types of non-coding transcripts. Out of the total number of transcripts differentially expressed we identify 80 upregulated and 181 down-regulated and we classify them as intergenic RNAs, antisense, processed transcripts, transcripts derived from pseudogenes and unassigned transcripts (Fig 5). The transcripts classified as “others” correspond to transcripts derived from miRNAs, rRNAs, sense-overlaping and sense intronic transcripts. The lncRNA annotation was performed with the Bioconductor package ChIPpeakAnno [40] and using Gencode v19 as reference [41]. The gene type corresponding to the gene that overlaps with the lincRNA locus was assigned to each lincRNA. Table 6 shows the top 25 non-coding transcripts regulated by SOX2 in GSCs.

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.