Sommario: 1. "Welfare senza risorse: emergenza o sistema. - 2. Economia reale e finanza speculativa. - 3. Eurozona e crisi globale. - 4. Solidariet\ue0 sociale e solidariet\ue0 familiare. - 5. Persona e salute. - 6. Vecchiaia e pensioni. - 7. Occupazione e ammortizzatori sociali. - 8. Previdenza e assistenza. - 9. "Welfare" ed autosufficienza. - 10. Sicurezza sociale e cittadinanza

Calvo, Tonantzin G.

Cañon, Estela

Cifdaloz, Metehan

Eyras, Eduardo

Graña, Osvaldo

Guo, Haihong

Gómez-López, Gonzalo

Kappes, Ferdinand

Karras, Panagiotis

Megías, Diego

Miñana, Belén

Muñoz, Javier

Olmeda, David

Ortiz-Romero, Pablo L.

Osterloh, Lisa

Riveiro-Falkenbach, Erica

Rodríguez-Peralto, Jose L.

Soengas, María S.

Tejedo, Cristina

Valcárcel, Juan

Ximénez-Embún, Pilar

Nature Communications

Publikationsserver der RWTH Aachen University

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

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

Grana, Osvaldo

Ximenez-Embun, Pilar

Munoz, Javier

Calvo, Tonantzin G

Minana, Belen

Gomez-Lopez, Gonzalo

Canon, Estela

Ortiz-Romero, Pablo L

Rodriguez-Peralto, Jose L

Megias, Diego

Valcarcel, Juan

Soengas, Maria S

University of Liverpool Repository

AbstractMelanomas 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.</jats:p

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

Crossref

RWTH Publications

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.The authors thank the colleagues in the CNIO Melanoma Group, in particular Eva Pérez-
Guijarro, Raúl Martinez, Ángel Colmenar, Direna Alonso-Curbelo and David Sáenz for
their help and support; Manuel Pérez from CNIO Confocal Microscopy Unit for
immunofluorescent image capture, and the i+12 Biobank of the Hospital 12 de Octubre
for providing melanoma patient samples. We also thank Endre Sebestyen for help with
genomic analyses of mRBPs in cancer cells; as well as José A Esteban (CBMSO, Madrid),
for critical reading of this manuscript. M.S.S. was funded by Marató TVE, Consolider
RNAREG (CSD2009-00080), and SAF2014-56868-R (Spanish Ministry of Economy and
Innovation). J.V. was funded by Fundación Botín, Banco de Santander through its
Santander Universities Global Division, Consolider RNAREG (CSD2009-00080),
AGAUR and the European Research Council, and acknowledges support of the Spanish
Ministry of Economy and Competitiveness, Centro de Excelencia Severo Ochoa 2013-
2017. J.L.R.-P. was funded by grant FIS 2014/1737, and P.L.O.-R. by FIS 14/1784 from
the Spanish Ministry of Health. E.E. was funded by grants BIO2011-23920, Consolider
RNAREG (CSD2009-00080), by AGAUR (2014-SGR1121) and by the Sandra Ibarra
Foundation for Cancer (FSI2013). The CNIO Proteomics Unit belongs to ProteoRed,
PRB2- ISCIII, supported by grant PT13/0001. J.M. was supported by the Ramon y Cajal
Programme (MINECO) RYC-2012-10651. H.G. and F.K. were funded by the China
Scholarship Council, the Deutsche Forschungsgemeinschaft (DFG KA 2799/1) and the
START Program of the Faculty of Medicine of the RWTH Aachen University. M.C. and
P.K. were funded by predoctoral fellowships from Fundación La Caixa, and C.T. from
SAF2014-56868-R. E.R.-F. was a recipient of a postdoctoral fellowship from
“FundaciónCientífica de la Asociación Española Contra el Cáncer”and was also supported by FMM-2013/0075 of Fundacion Mutua Madrileña.S

Graña Castro, Osvaldo

Muoz Peralta, Javier

Cañón, Estela

Rodríguez-Peralto, Jose L

Megias Vazquez, Diego

Soengas, MS

REPISALUD

English

Sommario: 1. "Welfare senza risorse: emergenza o sistema. - 2. Economia reale e finanza speculativa. - 3. Eurozona e crisi globale. - 4. Solidarietà sociale e solidarietà familiare. - 5. Persona e salute. - 6. Vecchiaia e pensioni. - 7. Occupazione e ammortizzatori sociali. - 8. Previdenza e assistenza. - 9. "Welfare" ed autosufficienza. - 10. Sicurezza sociale e cittadinanza

PESSI, ROBERTO

Archivio della ricerca- LUISS Libera Università Internazionale degli Studi Sociali Guido Carli di Roma

Ripensando il "welfare"

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.M.S.S. was funded by Marató TVE, Consolider RNAREG (CSD2009-00080), and SAF2014-56868-R (Spanish Ministry of Economy and Innovation). J.V. was funded by Fundación Botín, Banco de Santander through its Santander Universities Global Division, Consolider RNAREG (CSD2009-00080), AGAUR and the European Research Council, and acknowledges support of the Spanish Ministry of Economy and Competitiveness, Centro de Excelencia Severo Ochoa 2013-2017. J.L.R.-P. was funded by grant FIS 2014/1737, and P.L.O.-R. by FIS 14/1784 from the Spanish Ministry of Health. E.E. was funded by grants BIO2011-23920, Consolider RNAREG (CSD2009-00080), by AGAUR (2014-SGR1121) and by the Sandra Ibarra Foundation for Cancer (FSI2013). The CNIO Proteomics Unit belongs to ProteoRed, PRB2- ISCIII, supported by grant PT13/0001. J.M. was supported by the Ramon y Cajal Programme (MINECO) RYC-2012-10651. H.G. and F.K. were funded by the China Scholarship Council, the Deutsche Forschungsgemeinschaft (DFG KA 2799/1) and the START Program of the Faculty of Medicine of the RWTH Aachen University. M.C. and P.K. were funded by predoctoral fellowships from Fundación La Caixa, and C.T. from SAF2014-56868-R. E.R.-F. was a recipient of a postdoctoral fellowship from “Fundación Científica de la Asociación Española Contra el Cáncer” and was also supported by FMM-2013/0075 of Fundacion Mutua Madrileña

Ripensando il "welfare"

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