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oai:repisalud.isciii.es:20.500.12105/70152024-11-29T16:01:38Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Cifdaloz, Metehan author Osterloh, Lisa author Graña Castro, Osvaldo author Riveiro-Falkenbach, Erica author Ximenez-Embun, Pilar author Muoz Peralta, Javier author Tejedo, Cristina author Calvo, Tonantzin G author Karras, Panagiotis author Olmeda, David author Miñana, Belén author Gómez-López, Gonzalo author Cañón, Estela author Eyras, Eduardo author Guo, Haihong author Kappes, Ferdinand author Ortiz-Romero, Pablo L author Rodríguez-Peralto, Jose L author Megias Vazquez, Diego author Valcárcel, Juan author Soengas, MS author 2017 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. Nat Commun. 2017; 8(1):2249. 10.1038/s41467-017-02353-y 2041-1723 2041-1723 Nature communications 29269732 http://hdl.handle.net/20.500.12105/7015 Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1