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Title: RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis
Author: Sánchez Molina, Sara
Figuerola Bou, Elisabet
Blanco, Enrique
Sánchez Jiménez, María
Táboas, 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
Keywords: Sarcoma d'Ewing
Anomalies cromosòmiques
Ewing's sarcoma
Chromosome abnormalities
Issue Date: 1-Oct-2020
Publisher: American Association for the Advancement of Science
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Science Advances, 2020, vol. 6, num. 43
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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