microRNAs 424 and 503 are mediators of the anti-proliferative and anti-invasive action of the thyroid hormone receptor beta

The thyroid hormone receptors (TRs) mediate tumor suppressive effects in hepatocarcinoma and breast cancer cells. Here we show that incubation of hepatocarcinoma SK-hep1 cells expressing TRb with the thyroid hormone T3 induces transcription of the polycistronic message coding for microRNAs 424 and 5...

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Autores: Ruiz Llorente, Lidia, Ardila González, Soraya, Fanjul, Luisa F., Martínez Iglesias, Olaia, Aranda, Ana
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/662320
Acceso en línea:http://hdl.handle.net/10486/662320
Access Level:acceso abierto
Palabra clave:Thyroid hormone receptor
MicroRNA-424
MicroRNA-503
Proliferation
Invasion
Hepatocarcinoma and breast cancer cells
Biología y Biomedicina / Biología
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spelling microRNAs 424 and 503 are mediators of the anti-proliferative and anti-invasive action of the thyroid hormone receptor betaRuiz Llorente, LidiaArdila González, SorayaFanjul, Luisa F.Martínez Iglesias, OlaiaAranda, AnaThyroid hormone receptorMicroRNA-424MicroRNA-503ProliferationInvasionHepatocarcinoma and breast cancer cellsBiología y Biomedicina / BiologíaThe thyroid hormone receptors (TRs) mediate tumor suppressive effects in hepatocarcinoma and breast cancer cells. Here we show that incubation of hepatocarcinoma SK-hep1 cells expressing TRb with the thyroid hormone T3 induces transcription of the polycistronic message coding for microRNAs 424 and 503. TRb binds to the promoter region of these miRNAs and T3 induces an exchange of corepressors and coactivators inducing histone acetylation and transcriptional stimulation. We have validated cell cycle components as targets of these miRNAs. Overexpression of miR-424 mimicked the repressive effect of T3 on cell proliferation, growth in suspension, migration and invasion. Knockdown of miR-424 or miR-503 reduced the inhibitory effect of the hormone. T3 increased miR-424 and miR-503 in breast cancer cells expressing TRb, and this induction is also involved in the antiinvasive effects of the hormone. Furthermore, miR-424 or miR-503 depletion enhanced extravasation to the lungs of hepatocarcinoma cells injected in the tail vein of mice. The levels of these miRNAs were reduced in xenograft tumors formed in hypothyroid nude mice that are more invasive. Therefore, miR-424 or miR-503 mediate antiproliferative and anti-invasive actions of TRb both in cultured cells and in vivoThis work was supported by Grants from Ministerio de Economía y Competitividad BFU2011–28058, from the Instituto de Salud Carlos III RD12/0036/0030, and from the Comunidad de Madrid S2011/BMD-2328 (TIRONET).Impact JournalsInstituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)20142014-04-02research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/662320reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6623202026-06-23T12:46:27Z
dc.title.none.fl_str_mv microRNAs 424 and 503 are mediators of the anti-proliferative and anti-invasive action of the thyroid hormone receptor beta
title microRNAs 424 and 503 are mediators of the anti-proliferative and anti-invasive action of the thyroid hormone receptor beta
spellingShingle microRNAs 424 and 503 are mediators of the anti-proliferative and anti-invasive action of the thyroid hormone receptor beta
Ruiz Llorente, Lidia
Thyroid hormone receptor
MicroRNA-424
MicroRNA-503
Proliferation
Invasion
Hepatocarcinoma and breast cancer cells
Biología y Biomedicina / Biología
title_short microRNAs 424 and 503 are mediators of the anti-proliferative and anti-invasive action of the thyroid hormone receptor beta
title_full microRNAs 424 and 503 are mediators of the anti-proliferative and anti-invasive action of the thyroid hormone receptor beta
title_fullStr microRNAs 424 and 503 are mediators of the anti-proliferative and anti-invasive action of the thyroid hormone receptor beta
title_full_unstemmed microRNAs 424 and 503 are mediators of the anti-proliferative and anti-invasive action of the thyroid hormone receptor beta
title_sort microRNAs 424 and 503 are mediators of the anti-proliferative and anti-invasive action of the thyroid hormone receptor beta
dc.creator.none.fl_str_mv Ruiz Llorente, Lidia
Ardila González, Soraya
Fanjul, Luisa F.
Martínez Iglesias, Olaia
Aranda, Ana
author Ruiz Llorente, Lidia
author_facet Ruiz Llorente, Lidia
Ardila González, Soraya
Fanjul, Luisa F.
Martínez Iglesias, Olaia
Aranda, Ana
author_role author
author2 Ardila González, Soraya
Fanjul, Luisa F.
Martínez Iglesias, Olaia
Aranda, Ana
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)
dc.subject.none.fl_str_mv Thyroid hormone receptor
MicroRNA-424
MicroRNA-503
Proliferation
Invasion
Hepatocarcinoma and breast cancer cells
Biología y Biomedicina / Biología
topic Thyroid hormone receptor
MicroRNA-424
MicroRNA-503
Proliferation
Invasion
Hepatocarcinoma and breast cancer cells
Biología y Biomedicina / Biología
description The thyroid hormone receptors (TRs) mediate tumor suppressive effects in hepatocarcinoma and breast cancer cells. Here we show that incubation of hepatocarcinoma SK-hep1 cells expressing TRb with the thyroid hormone T3 induces transcription of the polycistronic message coding for microRNAs 424 and 503. TRb binds to the promoter region of these miRNAs and T3 induces an exchange of corepressors and coactivators inducing histone acetylation and transcriptional stimulation. We have validated cell cycle components as targets of these miRNAs. Overexpression of miR-424 mimicked the repressive effect of T3 on cell proliferation, growth in suspension, migration and invasion. Knockdown of miR-424 or miR-503 reduced the inhibitory effect of the hormone. T3 increased miR-424 and miR-503 in breast cancer cells expressing TRb, and this induction is also involved in the antiinvasive effects of the hormone. Furthermore, miR-424 or miR-503 depletion enhanced extravasation to the lungs of hepatocarcinoma cells injected in the tail vein of mice. The levels of these miRNAs were reduced in xenograft tumors formed in hypothyroid nude mice that are more invasive. Therefore, miR-424 or miR-503 mediate antiproliferative and anti-invasive actions of TRb both in cultured cells and in vivo
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-04-02
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/662320
url http://hdl.handle.net/10486/662320
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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