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Therapeutic Potential of EWSR1–FLI1 Inactivation by CRISPR/Cas9 in Ewing Sarcoma
dc.contributor.author | Cervera, Saint T. | |
dc.contributor.author | Rodríguez-Martín, Carlos | |
dc.contributor.author | Fernández-Tabanera, Enrique | |
dc.contributor.author | Melero-Fernández de Mera, Raquel Maria | |
dc.contributor.author | Morin, Matias | |
dc.contributor.author | Fernández-Peñalver, Sergio | |
dc.contributor.author | Iranzo-Martínez, Maria | |
dc.contributor.author | Amhih-Cardenas, Jorge | |
dc.contributor.author | García-García, Laura | |
dc.contributor.author | González-González, Laura | |
dc.contributor.author | Moreno-Pelayo, Miguel Angel | |
dc.contributor.author | Alonso, Javier | |
dc.date.accessioned | 2024-02-05T18:33:20Z | |
dc.date.available | 2024-02-05T18:33:20Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Cervera ST, Rodríguez-Martín C, Fernández-Tabanera E, Melero-Fernández de Mera RM, Morin M, Fernández-Peñalver S, Iranzo-Martínez M, Amhih-Cardenas J, García-García L, González-González L, Moreno-Pelayo MA, Alonso J. Therapeutic Potential of EWSR1-FLI1 Inactivation by CRISPR/Cas9 in Ewing Sarcoma. Cancers (Basel). 2021 Jul 27;13(15):3783. doi: 10.3390/cancers13153783. PMID: 34359682; PMCID: PMC8345183. | es |
dc.identifier.issn | 2072-6694 | |
dc.identifier.other | https://www.mdpi.com/2072-6694/13/15/3783 | es |
dc.identifier.uri | http://hdl.handle.net/20.500.12020/1204 | |
dc.description.abstract | Ewing sarcoma is an aggressive bone cancer affecting children and young adults. The main molecular hallmark of Ewing sarcoma are chromosomal translocations that produce chimeric oncogenic transcription factors, the most frequent of which is the aberrant transcription factor EWSR1–FLI1. Because this is the principal oncogenic driver of Ewing sarcoma, its inactivation should be the best therapeutic strategy to block tumor growth. In this study, we genetically inactivated EWSR1–FLI1 using CRISPR-Cas9 technology in order to cause permanent gene inactivation. We found that gene editing at the exon 9 of FLI1 was able to block cell proliferation drastically and induce senescence massively in the well-studied Ewing sarcoma cell line A673. In comparison with an extensively used cellular model of EWSR1–FLI1 knockdown (A673/TR/shEF), genetic inactivation was more effective, particularly in its capability to block cell proliferation. In summary, genetic inactivation of EWSR1–FLI1 in A673 Ewing sarcoma cells blocks cell proliferation and induces a senescence phenotype that could be exploited therapeutically. Although efficient and specific in vivo CRISPR-Cas9 editing still presents many challenges today, our data suggest that complete inactivation of EWSR1–FLI1 at the cell level should be considered a therapeutic approach to develop in the future. | es |
dc.description.sponsorship | This research was funded by the Instituto de Salud Carlos III, grant numbers PI20CIII/00020, DTS18CIII/00005, PI16CIII/00026; Asociación Pablo Ugarte, grant numbers TRPV205/18, TPI-M 1149/13; Asociación Candela Riera, Asociación Todos Somos Iván & Fundación Sonrisa de Alex, grant numbers TVP333-19, TVP-1324/15; ASION, grant number TVP141/17, and by the Spanish Center for Biomedical Network Research on Rare Diseases (CIBERER, ER19P5AC728/2021, grant to M.M.), and by the Regional Government of Madrid (CAM, B2017/BMD3721, grant to M.A.M.-P.). R.M.M-F.d.M. was supported by a grant from the Spanish Center for Biomedical Network Research on Rare Diseases (CIBERER). | es |
dc.language.iso | en | es |
dc.publisher | MDPI | es |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | Therapeutic Potential of EWSR1–FLI1 Inactivation by CRISPR/Cas9 in Ewing Sarcoma | es |
dc.type | article | es |
dc.identifier.doi | 10.3390/cancers13153783 | |
dc.issue.number | 15 | es |
dc.journal.title | Cancers | es |
dc.page.initial | 3783 | es |
dc.page.final | 3802 | es |
dc.rights.accessRights | openAccess | es |
dc.subject.area | Biología Celular y Molecular | es |
dc.subject.area | Ciencias Biomédicas | es |
dc.subject.keyword | Ewing sarcoma | es |
dc.subject.keyword | EWSR1–FLI1 | es |
dc.subject.keyword | CRISPR/Cas9 | es |
dc.subject.keyword | gene therapy | es |
dc.subject.keyword | cell cycle arrest | es |
dc.subject.keyword | senescence | es |
dc.volume.number | 13 | es |