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ZEB1 is a Subgroup-Specific Marker of Prognosis and Potential Drug Target in Medulloblastoma.
Fratini, Livia; Dalmolin, Matheus Gibeke Siqueira; Sinigaglia, Marialva; da Silveira Perla, Alexandre; de Farias, Caroline Brunetto; Brunetto, Algemir L; Brunetto, André T; da Cunha Jaeger, Mariane; Roesler, Rafael.
Afiliación
  • Fratini L; Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil. lidutra@hcpa.edu.br.
  • Dalmolin MGS; Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, 90050-170, Brazil. lidutra@hcpa.edu.br.
  • Sinigaglia M; Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre, RS, 91501-970, Brazil. lidutra@hcpa.edu.br.
  • da Silveira Perla A; Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil.
  • de Farias CB; Children's Cancer Institute, Porto Alegre, RS, 90620-110, Brazil.
  • Brunetto AL; Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil.
  • Brunetto AT; Children's Cancer Institute, Porto Alegre, RS, 90620-110, Brazil.
  • da Cunha Jaeger M; Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil.
  • Roesler R; Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, 90050-170, Brazil.
Neuromolecular Med ; 25(1): 64-74, 2023 03.
Article en En | MEDLINE | ID: mdl-35716340
ABSTRACT
Medulloblastoma (MB) is a malignant brain tumor that afflicts mostly children and adolescents and presents four distinct molecular subgroups, known as WNT, SHH, Group 3, and Group 4. ZEB1 is a transcription factor that promotes the expression of mesenchymal markers while restraining expression of epithelial and polarity genes. Because of ZEB1 involvement in cerebellum development, here we investigated the role of ZEB1 in MB. We found increased expression of ZEB1 in MB tumor samples compared to normal cerebellar tissue. Expression was higher in the SHH subgroup when compared to all other MB molecular subgroups. High ZEB1 expression was associated with poor prognosis in Group 3 and Group 4, whereas in patients with WNT tumors poorer prognosis were related to lower ZEB1 expression. There was a moderate correlation between ZEB1 and MYC expression in Group 3 and Group 4 MB. Treatment with the immunomodulator and histone deacetylase (HDAC) inhibitor fingolimod (FTY720) reduced ZEB1 expression specifically in D283 cells, which are representative of Group 3 and Group 4 MB. These findings reveal novel subgroup-specific associations of ZEB1 expression with survival in patients with MB and suggest that ZEB1 expression can be reduced by pharmacological agents that target HDAC activity.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Neoplasias Cerebelosas / Meduloblastoma Tipo de estudio: Prognostic_studies Idioma: En Revista: Neuromolecular Med Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2023 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Neoplasias Cerebelosas / Meduloblastoma Tipo de estudio: Prognostic_studies Idioma: En Revista: Neuromolecular Med Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2023 Tipo del documento: Article