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

Publication ,  Journal Article
Cifdaloz, M; Osterloh, L; Graña, O; Riveiro-Falkenbach, E; Ximénez-Embún, P; Muñoz, J; Tejedo, C; Calvo, TG; Karras, P; Olmeda, D; Miñana, B ...
Published in: Nature communications
December 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.

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Published In

Nature communications

DOI

EISSN

2041-1723

ISSN

2041-1723

Publication Date

December 2017

Volume

8

Issue

1

Start / End Page

2249

Related Subject Headings

  • Transcriptome
  • Systems Biology
  • Survival Analysis
  • RNA, Neoplasm
  • Proteomics
  • Prognosis
  • Poly-ADP-Ribose Binding Proteins
  • Oncogenes
  • Oncogene Proteins
  • Melanoma
 

Citation

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Cifdaloz, M., Osterloh, L., Graña, O., Riveiro-Falkenbach, E., Ximénez-Embún, P., Muñoz, J., … Soengas, M. S. (2017). Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1. Nature Communications, 8(1), 2249. https://doi.org/10.1038/s41467-017-02353-y
Cifdaloz, Metehan, Lisa Osterloh, Osvaldo Graña, Erica Riveiro-Falkenbach, Pilar Ximénez-Embún, Javier Muñoz, Cristina Tejedo, et al. “Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1.Nature Communications 8, no. 1 (December 2017): 2249. https://doi.org/10.1038/s41467-017-02353-y.
Cifdaloz M, Osterloh L, Graña O, Riveiro-Falkenbach E, Ximénez-Embún P, Muñoz J, et al. Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1. Nature communications. 2017 Dec;8(1):2249.
Cifdaloz, Metehan, et al. “Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1.Nature Communications, vol. 8, no. 1, Dec. 2017, p. 2249. Epmc, doi:10.1038/s41467-017-02353-y.
Cifdaloz M, Osterloh L, Graña O, Riveiro-Falkenbach E, Ximénez-Embún P, Muñoz J, Tejedo C, Calvo TG, Karras P, Olmeda D, Miñana B, Gómez-López G, Cañon E, Eyras E, Guo H, Kappes F, Ortiz-Romero PL, Rodríguez-Peralto JL, Megías D, Valcárcel J, Soengas MS. Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1. Nature communications. 2017 Dec;8(1):2249.

Published In

Nature communications

DOI

EISSN

2041-1723

ISSN

2041-1723

Publication Date

December 2017

Volume

8

Issue

1

Start / End Page

2249

Related Subject Headings

  • Transcriptome
  • Systems Biology
  • Survival Analysis
  • RNA, Neoplasm
  • Proteomics
  • Prognosis
  • Poly-ADP-Ribose Binding Proteins
  • Oncogenes
  • Oncogene Proteins
  • Melanoma