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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Detalles 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 recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/34531
Acceso en línea:http://hdl.handle.net/10230/34531
http://dx.doi.org/10.1038/s41467-017-02353-y
Access Level:acceso abierto
Palabra clave:Oncogenes
Binding proteins
Melanoma
CELF1 gene
Cultured cell line
Descripción
Sumario: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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