Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/197715
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dc.contributor.authorMartínez-Hernández, Rebecaes_ES
dc.contributor.authorSerrano-Somavilla, Anaes_ES
dc.contributor.authorRamos-Leví, Anaes_ES
dc.contributor.authorSampedro-Nuñez, Migueles_ES
dc.contributor.authorLens-Pardo, Albertoes_ES
dc.contributor.authorMuñoz De Nova, José Luises_ES
dc.contributor.authorTriviño, Juan Carloses_ES
dc.contributor.authorGonzález Sagardoy, María Ujuées_ES
dc.contributor.authorTorné, Lorenaes_ES
dc.contributor.authorCasares-Arias, Javieres_ES
dc.contributor.authorMartín-Cófreces, Noa B.es_ES
dc.contributor.authorSánchez-Madrid, Franciscoes_ES
dc.contributor.authorMarazuela, Mónicaes_ES
dc.date.accessioned2020-01-13T13:04:24Z-
dc.date.available2020-01-13T13:04:24Z-
dc.date.issued2019-12-
dc.identifier.citationEBioMedicine 50: 329-342 (2019)es_ES
dc.identifier.urihttp://hdl.handle.net/10261/197715-
dc.description.abstract[Background] The mechanisms underlying autoimmune thyroid disease (AITD) remain elusive. Identification of such mechanisms would reveal novel and/or better therapeutic targets. Here, we use integrated analysis of miRNAs and mRNAs expression profiling to identify potential therapeutic targets involved in the mechanisms underlying AITD.es_ES
dc.description.abstract[Methods] miRNA and mRNA from twenty fresh-frozen thyroid tissues (15 from AITD patients and 5 from healthy controls) were subjected to next-generation sequencing. An anti-correlated method revealed potential pathways and disease targets, including proteins involved in the formation of primary cilia. Thus, we examined the distribution and length of primary cilia in thyroid tissues from AITD and controls using immunofluorescence and scanning electron microscopy, and parsed cilia formation in thyroid cell lines in response to inflammatory stimuli in the presence of miRNA mimics.es_ES
dc.description.abstract[Findings] We found that the expression of miR-21-5p, miR-146b-3p, miR-5571-3p and miR-6503-3p was anti-correlated with Enolase 4 (ENO4), in-turned planar cell polarity protein (INTU), kinesin family member 27 (KIF27), parkin co-regulated (PACRG) and serine/threonine kinase 36 (STK36) genes. Functional classification of these miRNA/mRNAs revealed that their differential expression was associated with cilia organization. We demonstrated that the number and length of primary cilia in thyroid tissues was significantly lower in AITD than in control (frequency of follicular ciliated cells in controls = 67.54% vs a mean of 22.74% and 21.61% in HT and GD respectively p = 0.0001, by one-way ANOVA test). In addition, pro-inflammatory cytokines (IFNγ and TNFα) and specific miRNA mimics for the newly identified target genes affected cilia appearance in thyroid cell lines.es_ES
dc.description.abstract[Interpretation] Integrated miRNA/gene expression analysis has identified abnormal ciliogenesis as a novel susceptibility pathway that is involved in the pathogenesis of AITD. These results reflect that ciliogenesis plays a relevant role in AITD, and opens research pathways to design therapeutic targets in AITD.es_ES
dc.description.sponsorshipThis work was supported by the following grants: Proyectos de Investigación en Salud (FIS) PIE13-0041 and PI16-02091 (funded by Instituto de Salud Carlos III), TIRONET2-CM, B2017/BMD-3724 (funded by Comunidad de Madrid), GETNE G1707 (funded by Grupo Español de Tumores Neuroendocrinos y Endocrinos) and cofinanced by FEDER funds to MM. We also acknowledge the service from the MiNa Laboratory at IMN, and funding from CM (project S2018/NMT-4291 TEC2SPACE), MINECO (project CSIC13-4E-1794) and EU (FEDER, FSE) to M.U.G. The funders had no role in study design, data collection, data analysis, interpretation or writing of the report.es_ES
dc.language.isoenges_ES
dc.publisherElsevier BVes_ES
dc.relationS2017/BMD-3724/TIRONET2-CMes_ES
dc.relationS2018/NMT-4291/TEC2SPACE-CMes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rightsopenAccesses_ES
dc.subjectmicroRNAses_ES
dc.subjectmRNAes_ES
dc.subjectNext generation sequencinges_ES
dc.subjectAutoimmune thyroid diseasees_ES
dc.subjectGraves’ diseasees_ES
dc.subjectHashimoto's thyroiditises_ES
dc.subjectCiliaes_ES
dc.titleIntegrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseaseses_ES
dc.typeartículoes_ES
dc.identifier.doi10.1016/j.ebiom.2019.10.061-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.ebiom.2019.10.061es_ES
dc.identifier.e-issn2352-3964-
dc.rights.licensehttps://creativecommons.org/licenses/by-nc-nd/4.0/es_ES
dc.contributor.funderInstituto de Salud Carlos IIIes_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderGrupo Español de Tumores Neuroendocrinoses_ES
dc.contributor.funderEuropean Commissiones_ES
dc.contributor.funderConsejo Superior de Investigaciones Científicas (España)es_ES
dc.relation.csices_ES
oprm.item.hasRevisionno ko 0 false*
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003339es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100012818es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004587es_ES
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item.openairetypeartículo-
item.cerifentitytypePublications-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextopen-
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