Integrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseases
[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 involve...
| Autores: | , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/197715 |
| Acceso en línea: | http://hdl.handle.net/10261/197715 |
| Access Level: | acceso abierto |
| Palabra clave: | microRNAs mRNA Next generation sequencing Autoimmune thyroid disease Graves’ disease Hashimoto's thyroiditis Cilia |
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oai:digital.csic.es:10261/197715 |
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Integrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseasesMartínez-Hernández, RebecaSerrano-Somavilla, AnaRamos-Leví, AnaSampedro-Nuñez, MiguelLens-Pardo, AlbertoMuñoz De Nova, José LuisTriviño, Juan CarlosGonzález Sagardoy, María UjuéTorné, LorenaCasares-Arias, JavierMartín-Cófreces, Noa BeatrizSánchez-Madrid, FranciscoMarazuela, MónicamicroRNAsmRNANext generation sequencingAutoimmune thyroid diseaseGraves’ diseaseHashimoto's thyroiditisCilia[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.[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.[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.[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.This 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.Peer reviewedElsevier BVInstituto de Salud Carlos IIIComunidad de MadridGrupo Español de Tumores Neuroendocrinos y EndocrinosEuropean CommissionConsejo Superior de Investigaciones Científicas (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202020202019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/197715reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#S2017/BMD-3724/TIRONET2-CMS2018/NMT-4291/TEC2SPACE-CMhttps://doi.org/10.1016/j.ebiom.2019.10.061Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1977152026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
Integrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseases |
| title |
Integrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseases |
| spellingShingle |
Integrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseases Martínez-Hernández, Rebeca microRNAs mRNA Next generation sequencing Autoimmune thyroid disease Graves’ disease Hashimoto's thyroiditis Cilia |
| title_short |
Integrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseases |
| title_full |
Integrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseases |
| title_fullStr |
Integrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseases |
| title_full_unstemmed |
Integrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseases |
| title_sort |
Integrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseases |
| dc.creator.none.fl_str_mv |
Martínez-Hernández, Rebeca Serrano-Somavilla, Ana Ramos-Leví, Ana Sampedro-Nuñez, Miguel Lens-Pardo, Alberto Muñoz De Nova, José Luis Triviño, Juan Carlos González Sagardoy, María Ujué Torné, Lorena Casares-Arias, Javier Martín-Cófreces, Noa Beatriz Sánchez-Madrid, Francisco Marazuela, Mónica |
| author |
Martínez-Hernández, Rebeca |
| author_facet |
Martínez-Hernández, Rebeca Serrano-Somavilla, Ana Ramos-Leví, Ana Sampedro-Nuñez, Miguel Lens-Pardo, Alberto Muñoz De Nova, José Luis Triviño, Juan Carlos González Sagardoy, María Ujué Torné, Lorena Casares-Arias, Javier Martín-Cófreces, Noa Beatriz Sánchez-Madrid, Francisco Marazuela, Mónica |
| author_role |
author |
| author2 |
Serrano-Somavilla, Ana Ramos-Leví, Ana Sampedro-Nuñez, Miguel Lens-Pardo, Alberto Muñoz De Nova, José Luis Triviño, Juan Carlos González Sagardoy, María Ujué Torné, Lorena Casares-Arias, Javier Martín-Cófreces, Noa Beatriz Sánchez-Madrid, Francisco Marazuela, Mónica |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Instituto de Salud Carlos III Comunidad de Madrid Grupo Español de Tumores Neuroendocrinos y Endocrinos European Commission Consejo Superior de Investigaciones Científicas (España) Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
microRNAs mRNA Next generation sequencing Autoimmune thyroid disease Graves’ disease Hashimoto's thyroiditis Cilia |
| topic |
microRNAs mRNA Next generation sequencing Autoimmune thyroid disease Graves’ disease Hashimoto's thyroiditis Cilia |
| description |
[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. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2020 2020 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/197715 |
| url |
http://hdl.handle.net/10261/197715 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
#PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# S2017/BMD-3724/TIRONET2-CM S2018/NMT-4291/TEC2SPACE-CM https://doi.org/10.1016/j.ebiom.2019.10.061 Sí |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
Elsevier BV |
| publisher.none.fl_str_mv |
Elsevier BV |
| dc.source.none.fl_str_mv |
reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
| instname_str |
Consejo Superior de Investigaciones Científicas (CSIC) |
| reponame_str |
DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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1869416228269850624 |
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15,811543 |