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Musashi-1 regulates cell cycle and confers resistance to cisplatin treatment in Group 3/4 medulloblastomas cells.
Chagas, Pablo Shimaoka; Veronez, Luciana Chain; de Sousa, Graziella Ribeiro; Cruzeiro, Gustavo Alencastro Veiga; Corrêa, Carolina Alves Pereira; Saggioro, Fabiano Pinto; de Paula Queiroz, Rosane Gomes; Marie, Suely Kazue Nagahashi; Brandalise, Silvia Regina; Cardinalli, Izilda Aparecida; Yunes, José Andres; Júnior, Carlos Gilberto Carlotti; Machado, Hélio Rubens; Santos, Marcelo Volpon; Scrideli, Carlos Alberto; Tone, Luiz Gonzaga; Valera, Elvis Terci.
Afiliación
  • Chagas PS; Department of Genetics, Ribeirão Preto Medical School-University of São Paulo, Bandeirantes Avenue, 3900, Ribeirão Preto, São Paulo, 14048-900, Brazil. pablochagas@usp.br.
  • Veronez LC; Department of Pediatrics, Clinics Hospital-Ribeirão Preto Medical School-University of São Paulo, Ribeirão Preto, Brazil.
  • de Sousa GR; Department of Genetics, Ribeirão Preto Medical School-University of São Paulo, Bandeirantes Avenue, 3900, Ribeirão Preto, São Paulo, 14048-900, Brazil.
  • Cruzeiro GAV; Department of Pediatrics, Clinics Hospital-Ribeirão Preto Medical School-University of São Paulo, Ribeirão Preto, Brazil.
  • Corrêa CAP; Department of Pediatric Oncology, Harvard Medical School-Dana-Farber Cancer Institute, Boston, MA, USA.
  • Saggioro FP; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • de Paula Queiroz RG; Department of Pediatrics, Clinics Hospital-Ribeirão Preto Medical School-University of São Paulo, Ribeirão Preto, Brazil.
  • Marie SKN; Department of Pathology, Ribeirão Preto Medical School, 3900 Bandeirantes Avenue, Ribeirão Preto, SP, 14049-900, Brazil.
  • Brandalise SR; Department of Pathology, Rede D'Or São Luiz Hospital, Rua das Perobas, São Paulo, SP, 04321-120, Brazil.
  • Cardinalli IA; Department of Pediatrics, Clinics Hospital-Ribeirão Preto Medical School-University of São Paulo, Ribeirão Preto, Brazil.
  • Yunes JA; Laboratory of Cellular and Molecular Biology, Department of Neurology, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, SP, Brazil.
  • Júnior CGC; Boldrini's Children Center, Campinas, SP, Brazil.
  • Machado HR; Boldrini's Children Center, Campinas, SP, Brazil.
  • Santos MV; Boldrini's Children Center, Campinas, SP, Brazil.
  • Scrideli CA; Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo, São Paulo, Brazil.
  • Tone LG; Division of Pediatric Neurosurgery, Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • Valera ET; Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Bandeirantes Av., Ribeirão Preto, SP, 390014049-900, Brazil.
Hum Cell ; 36(6): 2129-2139, 2023 Nov.
Article en En | MEDLINE | ID: mdl-37460706
Groups (Grp) 3 and 4 are aggressive molecular subgroups of medulloblastoma (MB), with high rates of leptomeningeal dissemination. To date, there is still a paucity of biomarkers for these subtypes of MBs. In this study, we investigated the clinical significance and biological functions of Musashi-1 (MSI1) in Grp3 and Grp4-MBs. First, we assessed the expression profile of MSI1 in 59 primary MB samples (15-WNT, 18-SHH, 9-Grp3, and 17-Grp4 subgroups) by qRT-PCR. MSI1 mRNA expression levels were also validated in an additional public dataset of MBs (GSE85217). The ROC curve was used to validate the diagnostic standards of MSI1 expression. Next, the potential correlated cell-cycle genes were measured by RNA-Seq. Cell cycle, cell viability, and apoptosis were evaluated in a Grp3/Grp4 MB cell line after knockdown of MSI1 and cisplatin treatment. We identified an overexpression of MSI1 with a high accuracy to discriminate Grp3/Grp4-MBs from non-Grp3/Grp4-MBs. We identified that MSI1 knockdown not only triggered transcriptional changes in the cell-cycle pathway, but also affected G2/M phase in vitro, supporting the role of knockdown of MSI1 in cell-cycle arrest. Finally, MSI1 knockdown decreased cell viability and sensitized D283-Med cells to cisplatin treatment by enhancing cell apoptosis. Based on these findings, we suggest that MSI1 modulates cell-cycle progression and may play a role as biomarker for Grp3/Grp4-MBs. In addition, MSI1 knockdown combined with cisplatin may offer a potential strategy to be further explored in Grp3/Grp4-MBs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Guideline / Prognostic_studies Idioma: En Revista: Hum Cell Año: 2023 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Japón
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Guideline / Prognostic_studies Idioma: En Revista: Hum Cell Año: 2023 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Japón