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

التفاصيل البيبلوغرافية
العنوان: An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines
المؤلفون: Orla Sheils, John J. O'Leary, Salah A Elbaruni, Michael F Gallagher, Cathy Spillane, Praveen Sethupathy, Sebastian Vencken, Gordon Blackshields
المصدر: BMC Genomics
بيانات النشر: Springer Nature
مصطلحات موضوعية: Pluripotency, Pluripotent Stem Cells, Epithelial-Mesenchymal Transition, SOX2, Embryonic Development, Regulome, Biology, Cell Line, stomatognathic system, Cancer stem cell, Neoplasms, Genetics, Gene silencing, Humans, Gene Regulatory Networks, Gene Silencing, Induced pluripotent stem cell, Promoter Regions, Genetic, Embryonic Stem Cells, Binding Sites, microRNA, SOXB1 Transcription Factors, EMT, Embryonic stem cell, Cell biology, MicroRNAs, Cell Transformation, Neoplastic, Phenotype, Gene Expression Regulation, Embryonal carcinoma, Gene Knockdown Techniques, embryonic structures, Cancer research, Neoplastic Stem Cells, sense organs, Stem cell, biological phenomena, cell phenomena, and immunity, Adult stem cell, Research Article, Protein Binding, Biotechnology
الوصف: 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. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-711) contains supplementary material, which is available to authorized users.
اللغة: English
تدمد: 1471-2164
DOI: 10.1186/1471-2164-15-711
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::66ece9f57f14c5caecdaa8bde46707b6Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....66ece9f57f14c5caecdaa8bde46707b6
قاعدة البيانات: OpenAIRE
الوصف
تدمد:14712164
DOI:10.1186/1471-2164-15-711