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

BMC Genomics

Research Article

Praveen Sethupathy¹  Gordon Blackshields²  Cathy Spillane²  Salah Elbaruni²  Michael F Gallagher²  Orla Sheils²  Sebastian F Vencken²  John J O’Leary² 

[1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;Department of Histopathology, Trinity College Dublin, Sir Patrick Dun Research Laboratory, St. James’s Hospital, Dublin, Ireland;The Coombe Women and Infants University Hospital, Dublin, Ireland;

关键词: SOX2;    microRNA;    Embryonic stem cell;    Embryonal carcinoma;    Pluripotency;    EMT;   

DOI  :  10.1186/1471-2164-15-711

 received in 2014-01-12, accepted in 2014-07-15,  发布年份 2014

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Vencken et al.; licensee BioMed Central Ltd. 2014