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

Autor: García-García L; Unidad de Tumores Sólidos Infantiles, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain., Fernández-Tabanera E; Unidad de Tumores Sólidos Infantiles, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.; Centro de Investigación, Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, 28029 Madrid, Spain., Cervera ST; Unidad de Tumores Sólidos Infantiles, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.; Centro de Investigación, Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, 28029 Madrid, Spain., Melero-Fernández de Mera RM; Unidad de Tumores Sólidos Infantiles, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.; Centro de Investigación, Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, 28029 Madrid, Spain., Josa S; Unidad de Tumores Sólidos Infantiles, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain., González-González L; Unidad de Tumores Sólidos Infantiles, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain., Rodríguez-Martín C; Unidad de Tumores Sólidos Infantiles, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.; Centro de Investigación, Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, 28029 Madrid, Spain., Grünewald TGP; Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.; Hopp-Children's Cancer Center (KiTZ), 69120 Heidelberg, Germany.; Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany., Alonso J; Unidad de Tumores Sólidos Infantiles, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.; Centro de Investigación, Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, 28029 Madrid, Spain.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Nov 12; Vol. 13 (22). Date of Electronic Publication: 2021 Nov 12.
DOI: 10.3390/cancers13225668
Abstrakt: 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.
Databáze: MEDLINE
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