NDLI: The Transcription Factor FEZF1, a Direct Target of EWSR1-FLI1 in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Genes

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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

Content Provider	MDPI
Author	Laura, García-García Enrique, Fernández-Tabanera Laura, González-González Carlos, Rodríguez-Martín Thomas, G. P. Grünewald Cervera, Saint T. de Mera, Raquel M. Melero-Fernández Josa, Santiago Alonso, Javier
Copyright Year	2021
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.
Starting Page	5668
e-ISSN	20726694
DOI	10.3390/cancers13225668
Journal	Cancers
Issue Number	22
Volume Number	13
Language	English
Publisher	MDPI
Publisher Date	2021-11-12
Access Restriction	Open
Subject Keyword	Cancers Oncology Ewing Sarcoma Ewsr1-fli1 Ggaa-microsatellites Fezf11
Content Type	Text
Resource Type	Article

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