2026-04-17T20:00:44Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/1738082026-02-12T00:14:05Zcom_2072_1057col_2072_478916col_2072_478917
RECERCAT author Sánchez Molina, Sara author Figuerola Bou, Elisabet author Blanco, Enrique author Sánchez Jiménez, María author Táboas Outón, Pablo author Gómez, Soledad author Ballare, Cecilia author García Domínguez, Daniel J. author Prada, Estela author Hontecillas Prieto, Lourdes author Carcaboso, Ángel M. author Tirado, Oscar M. author Hernández Muñoz, Inmaculada author Álava, Enrique de author Lavarino, Cinzia author Croce, Luciano Di author Mora Salvador, Jaume 2021-02-09T10:19:45Z2021-02-09T10:19:45Z2020-10-012021-02-08T10:32:15Z 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. cc by-nc (c) Sánchez Molina et al., 2020 http://creativecommons.org/licenses/by-nc/3.0/es/ info:eu-repo/semantics/openAccess Sarcoma d'Ewing Anomalies cromosòmiques Ewing's sarcoma Chromosome abnormalities RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion