Revealing Temozolomide Resistance Mechanisms via Genome-Wide CRISPR Libraries

Registro completo de metadados
MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorButantan Institute-
Autor(es): dc.creatorRibeiro Reily Rocha, Clarissa-
Autor(es): dc.creatorReily Rocha, Alexandre [UNESP]-
Autor(es): dc.creatorMolina Silva, Matheus-
Autor(es): dc.creatorRodrigues Gomes, Luciana-
Autor(es): dc.creatorTeatin Latancia, Marcela-
Autor(es): dc.creatorAndrade Tomaz, Marina-
Autor(es): dc.creatorde Souza, Izadora-
Autor(es): dc.creatorKarolynne Seregni Monteiro, Linda-
Autor(es): dc.creatorFrederico Martins Menck, Carlos-
Data de aceite: dc.date.accessioned2022-02-22T00:48:38Z-
Data de disponibilização: dc.date.available2022-02-22T00:48:38Z-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2020-11-30-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/cells9122573-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/206922-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/206922-
Descrição: dc.descriptionGlioblastoma is a severe type of brain tumor with a poor prognosis and few therapy options. Temozolomide (TMZ) is one of these options, however, with limited success, and failure is mainly due to tumor resistance. In this work, genome-wide CRISPR-Cas9 lentiviral screen libraries for gene knockout or activation were transduced in the human glioblastoma cell line, aiming to identify genes that modulate TMZ resistance. The sgRNAs enriched in both libraries in surviving cells after TMZ treatment were identified by next-generation sequencing (NGS). Pathway analyses of gene candidates on knockout screening revealed several enriched pathways, including the mismatch repair and the Sonic Hedgehog pathways. Silencing three genes ranked on the top 10 list (MSH2, PTCH2, and CLCA2) confirm cell protection from TMZ-induced death. In addition, a CRISPR activation library revealed that NRF2 and Wnt pathways are involved in TMZ resistance. Consistently, overexpression of FZD6, CTNNB1, or NRF2 genes significantly increased cell survival upon TMZ treatment. Moreover, NRF2 and related genes detected in this screen presented a robust negative correlation with glioblastoma patient survival rates. Finally, several gene candidates from knockout or activation screening are targetable by inhibitors or small molecules, and some of them have already been used in the clinic.-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionDepartment of Clinical and Experimental Oncology Federal University of São Paulo (UNIFESP)-
Descrição: dc.descriptionInstitute of Theoretical Physics State University of São Paulo (UNESP)-
Descrição: dc.descriptionDepartment of Microbiology Institute of Biomedical Sciences University of São Paulo (USP)-
Descrição: dc.descriptionLaboratory of Cell Cycle Center of Toxins Immune Response and Cell Signaling (CeTICS) Butantan Institute-
Descrição: dc.descriptionInstitute of Theoretical Physics State University of São Paulo (UNESP)-
Descrição: dc.descriptionCAPES: 001-
Descrição: dc.descriptionCNPq: 308868/2018-8-
Idioma: dc.languageen-
Relação: dc.relationCells-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectcancer resistance-
Palavras-chave: dc.subjectCRISPR library-
Palavras-chave: dc.subjectglioblastoma-
Palavras-chave: dc.subjectNRF2-
Palavras-chave: dc.subjecttemozolomide-
Título: dc.titleRevealing Temozolomide Resistance Mechanisms via Genome-Wide CRISPR Libraries-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

Não existem arquivos associados a este item.