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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12-21

AUTHORS

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, María S. Soengas

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. More... »

PAGES

2249

References to SciGraph publications

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    8

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-017-02353-y

    DOI

    http://dx.doi.org/10.1038/s41467-017-02353-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1099729005

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29269732


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