title: Downregulation of Lnc-Spry1 mediates TGF-β-induced epithelial-mesenchymal transition by transcriptional and posttranscriptional regulatory mechanisms.
abstract: Long non-coding RNAs (lncRNAs) are a class of regulatory genes that participate in a wide range of biological processes, including proliferation, differentiation and development, as well as in a broad spectrum of diseases. Although the role of lncRNAs in TGF-β-induced epithelial-to-mesenchymal transition (EMT) has been well established, little is known about the role of lncRNAs as immediate-early regulators of EMT. Here lnc-Spry1 is identified as an immediate-early regulator of EMT that is downregulated by TGF-β. It is also found that knockdown of lnc-Spry1 promotes a mesenchymal-like phenotype and results in increased cell migration and invasion. In addition, it is shown that lnc-Spry1 depletion preferentially affects the expression of TGF-β-regulated gene targets. Moreover, lnc-Spry1 associates with U2AF65 splicing factor, suggesting a role in alternative splicing. Depletion of lnc-Spry1 induces, as TGF-β, isoform switching of fibroblast growth factor receptors, resulting in FGF-2-sensitive cells. Taken together, these results show that lnc-Spry1 could act as an early mediator of TGF-β signaling and reveal different roles for a lncRNA in modulating transcriptional and posttranscriptional gene expression.
authors.affiliation: Department of Cell Signaling, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER-CSIC), Avda Américo Vespucio s/n, Seville 41092, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez-Mateo
authors.affiliation: Department of Cell Signaling, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER-CSIC), Avda Américo Vespucio s/n, Seville 41092, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Torres
authors.affiliation: Department of Genetics, Seville University, Seville 41080, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gutiérrez
authors.affiliation: Department of Cell Signaling, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER-CSIC), Avda Américo Vespucio s/n, Seville 41092, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Pintor-Toro
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072668:Splicing Factor U2AF / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D010750:Phosphoproteins; D062085:RNA, Long Noncoding; D017468:Receptors, Fibroblast Growth Factor; D000072668:Splicing Factor U2AF; C425468:Spry1 protein, mouse; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2