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The transcription factor FEZF1, a direct target of EWSR1-FLI1 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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Main Authors: García-García, Laura (Author) , Fernández-Tabanera, Enrique (Author) , Cervera, Saint T. (Author) , Melero-Fernández de Mera, Raquel M. (Author) , Josa, Santiago (Author) , González-González, Laura (Author) , Rodríguez-Martín, Carlos (Author) , Grünewald, Thomas G. P. (Author) , Alonso, Javier (Author)
Format: Article (Journal)
Language:English
Published: 12 November 2021
In: Cancers
Year: 2021, Volume: 13, Issue: 22, Pages: 1-18
ISSN:2072-6694
DOI:10.3390/cancers13225668
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers13225668
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/13/22/5668
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Author Notes: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 and Javier Alonso
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Summary: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.
Item Description:Gesehen am 07.01.2022
Physical Description:Online Resource
ISSN:2072-6694
DOI:10.3390/cancers13225668

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