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

Metehan Cifdaloz, Lisa Osterloh, Osvaldo Graña, Erica Riveiro-Falkenbach, Pilar Ximénez-Embún, Javier Muñoz, Cristina Tejedo, Tonantzin G. Calvo, Panagiotis Karras, David Olmeda, Belén Miñana, Gonzalo Gómez-López, Estela Cañon, Eduardo Eyras, Haihong Guo, Ferdinand Kappes, Pablo L. Ortiz-Romero, Jose L. Rodríguez-Peralto, Diego Megías, Juan Valcárcel and María S. Soengas ()
Additional contact information
Metehan Cifdaloz: Spanish National Cancer Research Center (CNIO)
Lisa Osterloh: Spanish National Cancer Research Center (CNIO)
Osvaldo Graña: Bioinformatics Unit, CNIO
Erica Riveiro-Falkenbach: Universidad Complutense
Pilar Ximénez-Embún: Proteomics Core Unit, CNIO
Javier Muñoz: Proteomics Core Unit, CNIO
Cristina Tejedo: Spanish National Cancer Research Center (CNIO)
Tonantzin G. Calvo: Spanish National Cancer Research Center (CNIO)
Panagiotis Karras: Spanish National Cancer Research Center (CNIO)
David Olmeda: Spanish National Cancer Research Center (CNIO)
Belén Miñana: The Barcelona Institute of Science and Technology
Gonzalo Gómez-López: Bioinformatics Unit, CNIO
Estela Cañon: Spanish National Cancer Research Center (CNIO)
Eduardo Eyras: Universidad Pompeu Fabra
Haihong Guo: RWTH Aachen University
Ferdinand Kappes: RWTH Aachen University
Pablo L. Ortiz-Romero: Universidad Complutense
Jose L. Rodríguez-Peralto: Universidad Complutense
Diego Megías: Confocal Microscopy Unit, (CNIO)
Juan Valcárcel: The Barcelona Institute of Science and Technology
María S. Soengas: Spanish National Cancer Research Center (CNIO)

Nature Communications, 2017, vol. 8, issue 1, 1-18

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-02353-y

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