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.

CONCLUSION:

In ESC-like CSCs, SOX2 regulates a large miRNA network that regulates and interlinks the expression of crucial genes involved in EMT.

• Authors: Sebastian F Vencken, Praveen Sethupathy, Gordon Blackshields, Cathy Spillane, Salah Elbaruni, Orla Sheils, Michael F Gallagher, John J O'Leary
• Journal: BMC genomics (BMC Genomics) Vol. 15 Pg. 711 (Aug 25 2014) ISSN: 1471-2164 [Electronic] England
• PMID: 25156079 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MicroRNAs
• SOXB1 Transcription Factors

Topics

• Binding Sites
• Cell Line
• Cell Transformation, Neoplastic (genetics)
• Embryonic Development (genetics)
• Embryonic Stem Cells (metabolism)
• Epithelial-Mesenchymal Transition (genetics)
• Gene Expression Regulation
• Gene Knockdown Techniques
• Gene Regulatory Networks
• Gene Silencing
• Humans
• MicroRNAs (genetics)
• Neoplasms (genetics)
• Neoplastic Stem Cells (metabolism)
• Phenotype
• Pluripotent Stem Cells (metabolism)
• Promoter Regions, Genetic
• Protein Binding
• SOXB1 Transcription Factors (genetics)