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Nat Commun. 2017 Dec 21;8(1):2249. doi: 10.1038/s41467-017-02353-y.

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

Author information

1
Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), 28029, Madrid, Spain.
2
Bioinformatics Unit, CNIO, 28029, Madrid, Spain.
3
Instituto de Investigación i+12, Hospital 12 de Octubre Medical School, Universidad Complutense, 28041, Madrid, Spain.
4
Proteomics Core Unit, CNIO, Madrid, Spain.
5
Centre de Regulació Genòmica (CRG), The Barcelona Institute of Science and Technology, Barcelona, 08003, Spain.
6
Department of Experimental and Health Sciences, Universidad Pompeu Fabra, Barcelona, 08002, Spain.
7
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, 08010, Spain.
8
Institute of Biochemistry and Molecular Biology; Medical School, RWTH Aachen University, Aachen, 52074, Germany.
9
Department of Biological Sciences, Xi'an Jiaotong-Liverpool University, No. 111, Ren Ai Road, Dushu Lake Higher Education Town, Suzhou Industrial Park (SIP), Suzhou, 215123, China.
10
Confocal Microscopy Unit, (CNIO), Madrid, 28029, Spain.
11
Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), 28029, Madrid, Spain. msoengas@cnio.es.

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.

PMID:
29269732
PMCID:
PMC5740069
DOI:
10.1038/s41467-017-02353-y
[Indexed for MEDLINE]
Free PMC Article

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