An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines
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  • 作者：Sebastian F Vencken (1) (2)
    Praveen Sethupathy (3)
    Gordon Blackshields (1) (2)
    Cathy Spillane (1) (2)
    Salah Elbaruni (1) (2)
    Orla Sheils (1) (2)
    Michael F Gallagher (1) (2)
    John J O鈥橪eary (1) (2)

    1. Department of Histopathology     ; Trinity College Dublin ; Sir Patrick Dun Research Laboratory ; St. James鈥檚 Hospital ; Dublin ; Ireland
    2. The Coombe Women and Infants University Hospital     ; Dublin ; Ireland
    3. Department of Genetics     ; University of North Carolina at Chapel Hill ; Chapel Hill ; North Carolina ; USA
  • 关键词：SOX2 ; microRNA ; Embryonic stem cell ; Embryonal carcinoma ; Pluripotency ; EMT
  • 刊名：BMC Genomics
  • 出版年：2014
  • 出版时间：December 2014
  • 年：2014
  • 卷：15
  • 期：1
  • 全文大小：1,450 KB
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  • 刊物主题：Life Sciences, general; Microarrays; Proteomics; Animal Genetics and Genomics; Microbial Genetics and Genomics; Plant Genetics & Genomics;
  • 出版者：BioMed Central
  • ISSN：1471-2164
文摘
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.

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