Garcia-Garcia, LauraFernández-Tabanera, EnriqueCervera Mayor, Saint ThomasMelero-Fernández de Mera, Raquel MaríaJosa, SantiagoGonzalez-Gonzalez, LauraRodriguez-Martin, CarlosGrünewald, Thomas G PAlonso, Javier2021-12-202021-12-202021-11-12Cancers (Basel). 2021 Nov 12;13(22):5668.2072-6694http://hdl.handle.net/20.500.12105/13499Ewing 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.engVoRhttp://creativecommons.org/licenses/by/4.0/EWSR1-FLI1Ewing sarcomaFEZF11GGAA-microsatellitesAtribución 4.0 Internacional348308201322566810.3390/cancers13225668Cancersopen access