The Transcription Factor FEZF1, a Direct Target of EWSR1-FLI1 in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Genes
Identificadores
URI: http://hdl.handle.net/20.500.12020/1205ISSN: 2072-6694
DOI: 10.3390/CANCERS13225668
Autor/es
García García, Laura; Fernández Tabanera, Enrique; Cervera, Saint T; Melero Fernandez de Mera, Raquel Maria; Josa, Santiago; [et al.]Fecha
2021Tipo de documento
articleResumen
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 spe cific 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 knock down 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