title: An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines.
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.
  
  
  CONCLUSIONS
  In ESC-like CSCs, SOX2 regulates a large miRNA network that regulates and interlinks the expression of crucial genes involved in EMT.
authors.affiliation: Department of Histopathology, Trinity College Dublin, Sir Patrick Dun Research Laboratory, St, James's Hospital, Dublin, Ireland. venckens@tcd.ie.
authors.forename: Sebastian F
authors.initials: SF
authors.lastname: Vencken
authors.forename: Praveen
authors.initials: P
authors.lastname: Sethupathy
authors.forename: Gordon
authors.initials: G
authors.lastname: Blackshields
authors.forename: Cathy
authors.initials: C
authors.lastname: Spillane
authors.forename: Salah
authors.initials: S
authors.lastname: Elbaruni
authors.forename: Orla
authors.initials: O
authors.lastname: Sheils
authors.forename: Michael F
authors.initials: MF
authors.lastname: Gallagher
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Leary
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D055748:SOXB1 Transcription Factors / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D055748:SOXB1 Transcription Factors