title: miR-27 negatively regulates pluripotency-associated genes in human embryonal carcinoma cells.
abstract: Human embryonic stem cells and human embryonal carcinoma cells have been studied extensively with respect to the transcription factors (OCT4, SOX2 and NANOG), epigenetic modulators and associated signalling pathways that either promote self-renewal or induce differentiation in these cells. The ACTIVIN/NODAL axis (SMAD2/3) of the TGFß signalling pathway coupled with FGF signalling maintains self-renewal in these cells, whilst the BMP (SMAD1,5,8) axis promotes differentiation. Here we show that miR-27, a somatic-enriched miRNA, is activated upon RNAi-mediated suppression of OCT4 function in human embryonic stem cells. We further demonstrate that miR-27 negatively regulates the expression of the pluripotency-associated ACTIVIN/NODAL axis (SMAD2/3) of the TGFß signalling pathway by targeting ACVR2A, TGFßR1 and SMAD2. Additionally, we have identified a number of pluripotency-associated genes such as NANOG, LIN28, POLR3G and NR5A2 as novel miR-27 targets. Transcriptome analysis revealed that miR-27 over-expression in human embryonal carcinoma cells leads indeed to a significant up-regulation of genes involved in developmental pathways such as TGFß- and WNT-signalling.
authors.affiliation: Institute for Stem Cell Research and Regenerative Medicine, Faculty of Medicine, Heinrich Heine University, Duesseldorf, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Fuchs
authors.affiliation: Department of Vertebrate Genomics, Molecular Embryology and Aging Group, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Theuser
authors.affiliation: Institute for Stem Cell Research and Regenerative Medicine, Faculty of Medicine, Heinrich Heine University, Duesseldorf, Germany.
authors.forename: Wasco
authors.initials: W
authors.lastname: Wruck
authors.affiliation: Institute for Stem Cell Research and Regenerative Medicine, Faculty of Medicine, Heinrich Heine University, Duesseldorf, Germany; Department of Vertebrate Genomics, Molecular Embryology and Aging Group, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: James
authors.initials: J
authors.lastname: Adjaye
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D054278:Embryonal Carcinoma Stem Cells / Q000166:cytology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D015398:Signal Transduction; D051899:Smad2 Protein / Q000235:genetics; D015854:Up-Regulation
chemical_list: C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D017346:Protein Serine-Threonine Kinases; D030301:Activin Receptors, Type II; D000077293:Receptor, Transforming Growth Factor-beta Type I; C425585:activin receptor type II-A