Abstract
BackgroundSOX2 is a core component of the transcriptional network responsible for maintaining embryonal carcinoma cells (ECCs) in a pluripotent, undifferentiated state of self-renewal. As such, SOX2 is an oncogenic transcription factor and crucial cancer stem cell (CSC) biomarker in embryonal carcinoma and, as more recently found, in the stem-like cancer cell component of many other malignancies. SOX2 is furthermore a crucial factor in the maintenance of adult stem cell phenotypes and has additional roles in cell fate determination. The SOX2-linked microRNA (miRNA) transcriptome and regulome has not yet been fully defined in human pluripotent cells or CSCs. To improve our understanding of the SOX2-linked miRNA regulatory network as a contribution to the phenotype of these cell types, we used high-throughput differential miRNA and gene expression analysis combined with existing genome-wide SOX2 chromatin immunoprecipitation (ChIP) data to map the SOX2 miRNA transcriptome in two human embryonal carcinoma cell (hECC) lines.ResultsWhole-microRNAome and genome analysis of SOX2-silenced hECCs revealed many miRNAs regulated by SOX2, including several with highly characterised functions in both cancer and embryonic stem cell (ESC) biology. We subsequently performed genome-wide differential expression analysis and applied a Monte Carlo simulation algorithm and target prediction to identify a SOX2-linked miRNA regulome, which was strongly enriched with epithelial-to-mesenchymal transition (EMT) markers. Additionally, several deregulated miRNAs important to EMT processes had SOX2 binding sites in their promoter regions.ConclusionIn ESC-like CSCs, SOX2 regulates a large miRNA network that regulates and interlinks the expression of crucial genes involved in EMT.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-711) contains supplementary material, which is available to authorized users.
Highlights
SOX2 is a core component of the transcriptional network responsible for maintaining embryonal carcinoma cells (ECCs) in a pluripotent, undifferentiated state of self-renewal
Based on parameters set in our analysis we present several novel miRNAs that are direct transcriptional targets of SOX2
Successful knock-down was confirmed by comparing SOX2 mRNA and protein expression with cells transfected with a non-targeting control (Figure 1A and Figure 1B)
Summary
SOX2 is a core component of the transcriptional network responsible for maintaining embryonal carcinoma cells (ECCs) in a pluripotent, undifferentiated state of self-renewal. SOX2 is a member of the SRY-related HMG-box (SOX) transcription factor family with a set of well-established and diverse roles in stem cell potency and maintenance, embryonic development and cancer [1,2,3,4,5,6,7,8,9,10]. It regulates extensive and often divergent transcriptional networks across different cell types [1,2,11,12]. Many of the genes regulated by SOX2 in normal stem cells are aberrantly regulated by this transcription factor in cancerous cells with a similar, albeit malignant phenotype
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