title: Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal.
abstract: The embryonic stem cell (ESC) transcriptional and epigenetic networks are controlled by a multilayer regulatory circuitry, including core transcription factors (TFs), posttranscriptional modifier microRNAs (miRNAs), and some other regulators. However, the role of large intergenic noncoding RNAs (lincRNAs) in this regulatory circuitry and their underlying mechanism remains undefined. Here, we demonstrate that a lincRNA, linc-RoR, may function as a key competing endogenous RNA to link the network of miRNAs and core TFs, e.g., Oct4, Sox2, and Nanog. We show that linc-RoR shares miRNA-response elements with these core TFs and that linc-RoR prevents these core TFs from miRNA-mediated suppression in self-renewing human ESC. We suggest that linc-RoR forms a feedback loop with core TFs and miRNAs to regulate ESC maintenance and differentiation. These results may provide insights into the functional interactions of the components of genetic networks during development and may lead to new therapies for many diseases.
authors.affiliation: Department of Histology and Embryology, College of Basic Medicine, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Xu
authors.forename: Junfeng
authors.initials: J
authors.lastname: Jiang
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Kang
authors.forename: Lei
authors.initials: L
authors.lastname: Xiao
authors.forename: Minjuan
authors.initials: M
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Xiong
authors.forename: Xiaocan
authors.initials: X
authors.lastname: Guo
authors.forename: Houqi
authors.initials: H
authors.lastname: Liu
mesh_terms: D001665:Binding Sites; D002454:Cell Differentiation; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020871:RNA Stability; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D050436:Regulatory Elements, Transcriptional; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D018398:Homeodomain Proteins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D062085:RNA, Long Noncoding; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases