An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines

Hdl Handle:
http://hdl.handle.net/10147/326185
Title:
An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines
Authors:
Vencken, Sebastian F; Sethupathy, Praveen; Blackshields, Gordon; Spillane, Cathy; Elbaruni, Salah; Sheils, Orla; Gallagher, Michael F; O’Leary, John J
Citation:
Vencken SF et al. An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines. BMC Genomics. 2014 Aug 25;15(1):711
Issue Date:
25-Aug-2014
URI:
http://dx.doi.org/10.1186/1471-2164-15-711; http://hdl.handle.net/10147/326185
Abstract:
Abstract Background SOX2 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. Results Whole-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. Conclusion In ESC-like CSCs, SOX2 regulates a large miRNA network that regulates and interlinks the expression of crucial genes involved in EMT.
Language:
en
Keywords:
GENETICS; CANCER
Local subject classification:
STEM CELLS

Full metadata record

DC FieldValue Language
dc.contributor.authorVencken, Sebastian Fen_GB
dc.contributor.authorSethupathy, Praveenen_GB
dc.contributor.authorBlackshields, Gordonen_GB
dc.contributor.authorSpillane, Cathyen_GB
dc.contributor.authorElbaruni, Salahen_GB
dc.contributor.authorSheils, Orlaen_GB
dc.contributor.authorGallagher, Michael Fen_GB
dc.contributor.authorO’Leary, John Jen_GB
dc.date.accessioned2014-09-17T08:57:11Z-
dc.date.available2014-09-17T08:57:11Z-
dc.date.issued2014-08-25-
dc.identifier.citationVencken SF et al. An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines. BMC Genomics. 2014 Aug 25;15(1):711en_GB
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2164-15-711-
dc.identifier.urihttp://hdl.handle.net/10147/326185-
dc.description.abstractAbstract Background SOX2 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. Results Whole-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. Conclusion In ESC-like CSCs, SOX2 regulates a large miRNA network that regulates and interlinks the expression of crucial genes involved in EMT.-
dc.language.isoenen
dc.subjectGENETICSen_GB
dc.subjectCANCERen_GB
dc.subject.otherSTEM CELLSen_GB
dc.titleAn integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell linesen_GB
dc.language.rfc3066en-
dc.rights.holderSebastian F Vencken et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2014-09-10T11:02:45Z-
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