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; María S. Soengas

doi:10.1038/s41467-017-02353-y

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 ValcárcelMaría S. Soengas^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

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.

Original language	English
Article number	2249
Journal	Nature Communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-02353-y
Publication status	Published - 1 Dec 2017
Externally published	Yes

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Cifdaloz, M., Osterloh, L., Graña, O., Riveiro-Falkenbach, E., Ximénez-Embún, P., Muñoz, J., Tejedo, C., Calvo, T. G., Karras, P., Olmeda, D., Miñana, B., Gómez-López, G., Cañon, E., Eyras, E., Guo, H., Kappes, F., Ortiz-Romero, P. L., Rodríguez-Peralto, J. L., Megías, D., ... Soengas, M. S. (2017). Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1. Nature Communications, 8(1), Article 2249. https://doi.org/10.1038/s41467-017-02353-y

@article{5fe391e69bda41af8364fab9b8fba8a8,

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

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.",

author = "Metehan Cifdaloz and Lisa Osterloh and Osvaldo Gra{\~n}a and Erica Riveiro-Falkenbach and Pilar Xim{\'e}nez-Emb{\'u}n and Javier Mu{\~n}oz and Cristina Tejedo and Calvo, {Tonantzin G.} and Panagiotis Karras and David Olmeda and Bel{\'e}n Mi{\~n}ana and Gonzalo G{\'o}mez-L{\'o}pez and Estela Ca{\~n}on and Eduardo Eyras and Haihong Guo and Ferdinand Kappes and Ortiz-Romero, {Pablo L.} and Rodr{\'i}guez-Peralto, {Jose L.} and Diego Meg{\'i}as and Juan Valc{\'a}rcel and Soengas, {Mar{\'i}a S.}",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/s41467-017-02353-y",

language = "English",

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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 2017, 'Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1', Nature Communications, vol. 8, no. 1, 2249. https://doi.org/10.1038/s41467-017-02353-y

TY - JOUR

T1 - Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1

AU - Cifdaloz, Metehan

AU - Osterloh, Lisa

AU - Graña, Osvaldo

AU - Riveiro-Falkenbach, Erica

AU - Ximénez-Embún, Pilar

AU - Muñoz, Javier

AU - Tejedo, Cristina

AU - Calvo, Tonantzin G.

AU - Karras, Panagiotis

AU - Olmeda, David

AU - Miñana, Belén

AU - Gómez-López, Gonzalo

AU - Cañon, Estela

AU - Eyras, Eduardo

AU - Guo, Haihong

AU - Kappes, Ferdinand

AU - Ortiz-Romero, Pablo L.

AU - Rodríguez-Peralto, Jose L.

AU - Megías, Diego

AU - Valcárcel, Juan

AU - Soengas, María S.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85042387158&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-02353-y

DO - 10.1038/s41467-017-02353-y

M3 - Article

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2249

ER -

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

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