RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis

Ewing sarcoma (EwS) is an aggressive tumor that affects adolescents and young adults. EwS is defined by a chromosomal translocation, EWSR1-FLI1 being the most common, that causes genome reprogramming through remodeling of enhancers. Here, we describe an unexpected function of RING1B, which is highly...

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Autores: Sánchez Molina, Sara, Figuerola Bou, Elisabet, Blanco, Enrique, Sánchez Jiménez, María, Táboas Outón, Pablo, Gómez, Soledad, Ballare, Cecilia, García Domínguez, Daniel J., Prada, Estela, Hontecillas Prieto, Lourdes, Carcaboso, Ángel M., Tirado, Oscar M., Hernández Muñoz, Inmaculada, Álava, Enrique de, Lavarino, Cinzia, Croce, Luciano Di, Mora Salvador, Jaume
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/173808
Acceso en línea:https://hdl.handle.net/2445/173808
Access Level:acceso abierto
Palabra clave:Sarcoma d'Ewing
Anomalies cromosòmiques
Ewing's sarcoma
Chromosome abnormalities
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spelling RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesisSánchez Molina, SaraFiguerola Bou, ElisabetBlanco, EnriqueSánchez Jiménez, MaríaTáboas Outón, PabloGómez, SoledadBallare, CeciliaGarcía Domínguez, Daniel J.Prada, EstelaHontecillas Prieto, LourdesCarcaboso, Ángel M.Tirado, Oscar M.Hernández Muñoz, InmaculadaÁlava, Enrique deLavarino, CinziaCroce, Luciano DiMora Salvador, JaumeSarcoma d'EwingAnomalies cromosòmiquesEwing's sarcomaChromosome abnormalitiesEwing sarcoma (EwS) is an aggressive tumor that affects adolescents and young adults. EwS is defined by a chromosomal translocation, EWSR1-FLI1 being the most common, that causes genome reprogramming through remodeling of enhancers. Here, we describe an unexpected function of RING1B, which is highly expressed in EwS. While retaining its repressive activity at Polycomb developmental regulated genes, RING1B colocalizes with EWSR1-FLI1 at active enhancers. We demonstrate that RING1B is necessary for the expression of key EWSR1-FLI1 targets by facilitating oncogene recruitment to their enhancers. Knockdown of RING1B impairs growth of tumor xenografts and expression of genes regulated by EWSR1-FLI1 bound enhancers. Pharmacological inhibition of AURKB with AZD1152 increases H2Aub levels causing down-regulation of RING1B/ EWSR1-FLI1 common targets. Our findings demonstrate that RING1B is a critical modulator of EWSR1-FLI1-induced chromatin remodeling, and its inhibition is a potential therapeutic strategy for the treatment of these tumors.American Association for the Advancement of Science2021202120202021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion16 p.application/pdfhttps://hdl.handle.net/2445/173808Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1126/sciadv.aba3058Science Advances, 2020, vol. 6, num. 43https://doi.org/10.1126/sciadv.aba3058cc by-nc (c) Sánchez Molina et al., 2020http://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1738082026-05-29T05:05:01Z
dc.title.none.fl_str_mv RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis
title RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis
spellingShingle RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis
Sánchez Molina, Sara
Sarcoma d'Ewing
Anomalies cromosòmiques
Ewing's sarcoma
Chromosome abnormalities
title_short RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis
title_full RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis
title_fullStr RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis
title_full_unstemmed RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis
title_sort RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis
dc.creator.none.fl_str_mv Sánchez Molina, Sara
Figuerola Bou, Elisabet
Blanco, Enrique
Sánchez Jiménez, María
Táboas Outón, Pablo
Gómez, Soledad
Ballare, Cecilia
García Domínguez, Daniel J.
Prada, Estela
Hontecillas Prieto, Lourdes
Carcaboso, Ángel M.
Tirado, Oscar M.
Hernández Muñoz, Inmaculada
Álava, Enrique de
Lavarino, Cinzia
Croce, Luciano Di
Mora Salvador, Jaume
author Sánchez Molina, Sara
author_facet Sánchez Molina, Sara
Figuerola Bou, Elisabet
Blanco, Enrique
Sánchez Jiménez, María
Táboas Outón, Pablo
Gómez, Soledad
Ballare, Cecilia
García Domínguez, Daniel J.
Prada, Estela
Hontecillas Prieto, Lourdes
Carcaboso, Ángel M.
Tirado, Oscar M.
Hernández Muñoz, Inmaculada
Álava, Enrique de
Lavarino, Cinzia
Croce, Luciano Di
Mora Salvador, Jaume
author_role author
author2 Figuerola Bou, Elisabet
Blanco, Enrique
Sánchez Jiménez, María
Táboas Outón, Pablo
Gómez, Soledad
Ballare, Cecilia
García Domínguez, Daniel J.
Prada, Estela
Hontecillas Prieto, Lourdes
Carcaboso, Ángel M.
Tirado, Oscar M.
Hernández Muñoz, Inmaculada
Álava, Enrique de
Lavarino, Cinzia
Croce, Luciano Di
Mora Salvador, Jaume
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Sarcoma d'Ewing
Anomalies cromosòmiques
Ewing's sarcoma
Chromosome abnormalities
topic Sarcoma d'Ewing
Anomalies cromosòmiques
Ewing's sarcoma
Chromosome abnormalities
description Ewing sarcoma (EwS) is an aggressive tumor that affects adolescents and young adults. EwS is defined by a chromosomal translocation, EWSR1-FLI1 being the most common, that causes genome reprogramming through remodeling of enhancers. Here, we describe an unexpected function of RING1B, which is highly expressed in EwS. While retaining its repressive activity at Polycomb developmental regulated genes, RING1B colocalizes with EWSR1-FLI1 at active enhancers. We demonstrate that RING1B is necessary for the expression of key EWSR1-FLI1 targets by facilitating oncogene recruitment to their enhancers. Knockdown of RING1B impairs growth of tumor xenografts and expression of genes regulated by EWSR1-FLI1 bound enhancers. Pharmacological inhibition of AURKB with AZD1152 increases H2Aub levels causing down-regulation of RING1B/ EWSR1-FLI1 common targets. Our findings demonstrate that RING1B is a critical modulator of EWSR1-FLI1-induced chromatin remodeling, and its inhibition is a potential therapeutic strategy for the treatment of these tumors.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/173808
url https://hdl.handle.net/2445/173808
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1126/sciadv.aba3058
Science Advances, 2020, vol. 6, num. 43
https://doi.org/10.1126/sciadv.aba3058
dc.rights.none.fl_str_mv cc by-nc (c) Sánchez Molina et al., 2020
http://creativecommons.org/licenses/by-nc/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc (c) Sánchez Molina et al., 2020
http://creativecommons.org/licenses/by-nc/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 16 p.
application/pdf
dc.publisher.none.fl_str_mv American Association for the Advancement of Science
publisher.none.fl_str_mv American Association for the Advancement of Science
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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