Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1

Melanomas are well-known for their altered mRNA expression profiles. Yet, the specific contribution of mRNA binding proteins (mRBPs) to melanoma development remains unclear. Here we identify a cluster of melanoma-enriched genes under the control of CUGBP Elav-like family member 1 (CELF1). CELF1 was...

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Detalhes bibliográficos
Autores: Cifdaloz, Metehan, Osterloh, Lisa, Graña-Castro, Osvaldo, Riveiro-Falkenbach, Erica, Ximénez-Embún, Pilar, Muñoz, Javier, Tejedo, Cristina, Calvo, Tonantzin G., Karras, Panagiotis, Olmeda, David, Miñana Gómez, Belén, Gómez López, Gonzalo, Cañón, Estela, Eyras Jiménez, Eduardo, Guo, Haihong, Kappes, Ferdinand, Ortíz Romero, Pablo Luis, Rodríguez Peraltó, José Luís, Megías, Diego, Valcárcel, J. (Juan), Soengas, María S.
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2017
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/34531
Acesso em linha:http://hdl.handle.net/10230/34531
http://dx.doi.org/10.1038/s41467-017-02353-y
Access Level:Acceso aberto
Palavra-chave:Oncogenes
Binding proteins
Melanoma
CELF1 gene
Cultured cell line
Descrição
Resumo:Melanomas are well-known for their altered mRNA expression profiles. Yet, the specific contribution of mRNA binding proteins (mRBPs) to melanoma development remains unclear. Here we identify a cluster of melanoma-enriched genes under the control of CUGBP Elav-like family member 1 (CELF1). CELF1 was discovered with a distinct prognostic value in melanoma after mining the genomic landscape of the 692 known mRBPs across different cancer types. Genome-wide transcriptomic, proteomic, and RNA-immunoprecipitation studies, together with loss-of-function analyses in cell lines, and histopathological evaluation in clinical biopsies, revealed an intricate repertoire of CELF1-RNA interactors with minimal overlap with other malignancies. This systems approach uncovered the oncogene DEK as an unexpected target and downstream effector of CELF1. Importantly, CELF1 and DEK were found to represent early-induced melanoma genes and adverse indicators of overall patient survival. These results underscore novel roles of CELF1 in melanoma, illustrating tumor type-restricted functions of RBPs in cancer.

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