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, Ximenez-Embun, Pilar, Muoz Peralta, Javier, Tejedo, Cristina, Calvo, Tonantzin G, Karras, Panagiotis, Olmeda, David, Miñana, Belén, Gómez-López, Gonzalo, Cañón, Estela, Eyras, Eduardo, Guo, Haihong, Kappes, Ferdinand, Ortiz-Romero, Pablo L, Rodríguez-Peralto, Jose L, Megias Vazquez, Diego, Valcárcel, Juan, Soengas, MS
Formato: artículo
Fecha de publicación:2017
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/7015
Acesso em linha:http://hdl.handle.net/20.500.12105/7015
Access Level:acceso abierto
Palavra-chave:3' Untranslated Regions
Biopsy
CELF1 Protein
Cell Line, Tumor
Cell Proliferation
Chromosomal Proteins, Non-Histone
Humans
Immunoprecipitation
Melanoma
Oncogene Proteins
Poly-ADP-Ribose Binding Proteins
Prognosis
Proteomics
RNA, Neoplasm
Survival Analysis
Transcriptome
Oncogenes
Systems Biology
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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