The Transcription Factor <i>FEZF1</i>, a Direct Target of <i>EWSR1-FLI1</i> in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Genes

Ewing sarcoma is a rare pediatric tumor characterized by chromosomal translocations that give rise to aberrant chimeric transcription factors (e.g., EWSR1-FLI1). EWSR1-FLI1 promotes a specific cellular transcriptional program. Therefore, the study of EWSR1-FLI1 target genes is important to identify...

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Autores principales:	Laura García-García, Enrique Fernández-Tabanera, Saint T. Cervera, Raquel M. Melero-Fernández de Mera, Santiago Josa, Laura González-González, Carlos Rodríguez-Martín, Thomas G. P. Grünewald, Javier Alonso
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Ewing sarcoma EWSR1-FLI1 GGAA-microsatellites FEZF11 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/450bda7000bf4efe980287f86f1a4f68
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spelling	oai:doaj.org-article:450bda7000bf4efe980287f86f1a4f682021-11-25T17:02:24ZThe Transcription Factor <i>FEZF1</i>, a Direct Target of <i>EWSR1-FLI1</i> in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Genes10.3390/cancers132256682072-6694https://doaj.org/article/450bda7000bf4efe980287f86f1a4f682021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5668https://doaj.org/toc/2072-6694Ewing sarcoma is a rare pediatric tumor characterized by chromosomal translocations that give rise to aberrant chimeric transcription factors (e.g., EWSR1-FLI1). EWSR1-FLI1 promotes a specific cellular transcriptional program. Therefore, the study of EWSR1-FLI1 target genes is important to identify critical pathways involved in Ewing sarcoma tumorigenesis. In this work, we focused on the transcription factors regulated by EWSR1-FLI1 in Ewing sarcoma. Transcriptomic analysis of the Ewing sarcoma cell line A673 indicated that one of the genes more strongly upregulated by EWSR1-FLI1 was FEZF1 (FEZ family zinc finger protein 1), a transcriptional repressor involved in neural cell identity. The functional characterization of FEZF1 was performed in three Ewing sarcoma cell lines (A673, SK-N-MC, SK-ES-1) through an shRNA-directed silencing approach. FEZF1 knockdown inhibited clonogenicity and cell proliferation. Finally, the analysis of the FEZF1-dependent expression profile in A673 cells showed several neural genes regulated by FEZF1 and concomitantly regulated by EWSR1-FLI1. In summary, FEZF1 is transcriptionally regulated by EWSR1-FLI1 in Ewing sarcoma cells and is involved in the regulation of neural-specific genes, which could explain the neural-like phenotype observed in several Ewing sarcoma tumors and cell lines.Laura García-GarcíaEnrique Fernández-TabaneraSaint T. CerveraRaquel M. Melero-Fernández de MeraSantiago JosaLaura González-GonzálezCarlos Rodríguez-MartínThomas G. P. GrünewaldJavier AlonsoMDPI AGarticleEwing sarcomaEWSR1-FLI1GGAA-microsatellitesFEZF11Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5668, p 5668 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ewing sarcoma EWSR1-FLI1 GGAA-microsatellites FEZF11 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Ewing sarcoma EWSR1-FLI1 GGAA-microsatellites FEZF11 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Laura García-García Enrique Fernández-Tabanera Saint T. Cervera Raquel M. Melero-Fernández de Mera Santiago Josa Laura González-González Carlos Rodríguez-Martín Thomas G. P. Grünewald Javier Alonso The Transcription Factor <i>FEZF1</i>, a Direct Target of <i>EWSR1-FLI1</i> in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Genes
description	Ewing sarcoma is a rare pediatric tumor characterized by chromosomal translocations that give rise to aberrant chimeric transcription factors (e.g., EWSR1-FLI1). EWSR1-FLI1 promotes a specific cellular transcriptional program. Therefore, the study of EWSR1-FLI1 target genes is important to identify critical pathways involved in Ewing sarcoma tumorigenesis. In this work, we focused on the transcription factors regulated by EWSR1-FLI1 in Ewing sarcoma. Transcriptomic analysis of the Ewing sarcoma cell line A673 indicated that one of the genes more strongly upregulated by EWSR1-FLI1 was FEZF1 (FEZ family zinc finger protein 1), a transcriptional repressor involved in neural cell identity. The functional characterization of FEZF1 was performed in three Ewing sarcoma cell lines (A673, SK-N-MC, SK-ES-1) through an shRNA-directed silencing approach. FEZF1 knockdown inhibited clonogenicity and cell proliferation. Finally, the analysis of the FEZF1-dependent expression profile in A673 cells showed several neural genes regulated by FEZF1 and concomitantly regulated by EWSR1-FLI1. In summary, FEZF1 is transcriptionally regulated by EWSR1-FLI1 in Ewing sarcoma cells and is involved in the regulation of neural-specific genes, which could explain the neural-like phenotype observed in several Ewing sarcoma tumors and cell lines.
format	article
author	Laura García-García Enrique Fernández-Tabanera Saint T. Cervera Raquel M. Melero-Fernández de Mera Santiago Josa Laura González-González Carlos Rodríguez-Martín Thomas G. P. Grünewald Javier Alonso
author_facet	Laura García-García Enrique Fernández-Tabanera Saint T. Cervera Raquel M. Melero-Fernández de Mera Santiago Josa Laura González-González Carlos Rodríguez-Martín Thomas G. P. Grünewald Javier Alonso
author_sort	Laura García-García
title	The Transcription Factor <i>FEZF1</i>, a Direct Target of <i>EWSR1-FLI1</i> in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Genes
title_short	The Transcription Factor <i>FEZF1</i>, a Direct Target of <i>EWSR1-FLI1</i> in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Genes
title_full	The Transcription Factor <i>FEZF1</i>, a Direct Target of <i>EWSR1-FLI1</i> in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Genes
title_fullStr	The Transcription Factor <i>FEZF1</i>, a Direct Target of <i>EWSR1-FLI1</i> in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Genes
title_full_unstemmed	The Transcription Factor <i>FEZF1</i>, a Direct Target of <i>EWSR1-FLI1</i> in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Genes
title_sort	transcription factor <i>fezf1</i>, a direct target of <i>ewsr1-fli1</i> in ewing sarcoma cells, regulates the expression of neural-specific genes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/450bda7000bf4efe980287f86f1a4f68
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The Transcription Factor <i>FEZF1</i>, a Direct Target of <i>EWSR1-FLI1</i> in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Genes

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