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c-Jun-N-terminal phosphorylation regulates DNMT1 expression and genome wide methylation in gliomas.
Heiland, Dieter H; Ferrarese, Roberto; Claus, Rainer; Dai, Fangping; Masilamani, Anie P; Kling, Eva; Weyerbrock, Astrid; Kling, Teresia; Nelander, Sven; Carro, Maria S.
Afiliación
  • Heiland DH; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.
  • Ferrarese R; Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Claus R; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.
  • Dai F; Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Masilamani AP; Department of Hematology, Oncology, and Stem Cell Transplantation, University of Freiburg Medical Center, Freiburg, Germany.
  • Kling E; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.
  • Weyerbrock A; Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Kling T; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.
  • Nelander S; Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Carro MS; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.
Oncotarget ; 8(4): 6940-6954, 2017 Jan 24.
Article en En | MEDLINE | ID: mdl-28036297
High-grade gliomas (HGG) are the most common brain tumors, with an average survival time of 14 months. A glioma-CpG island methylator phenotype (G-CIMP), associated with better clinical outcome, has been described in low and high-grade gliomas. Mutation of IDH1 is known to drive the G-CIMP status. In some cases, however, the hypermethylation phenotype is independent of IDH1 mutation, suggesting the involvement of other mechanisms. Here, we demonstrate that DNMT1 expression is higher in low-grade gliomas compared to glioblastomas and correlates with phosphorylated c-Jun. We show that phospho-c-Jun binds to the DNMT1 promoter and causes DNA hypermethylation. Phospho-c-Jun activation by Anisomycin treatment in primary glioblastoma-derived cells attenuates the aggressive features of mesenchymal glioblastomas and leads to promoter methylation and downregulation of key mesenchymal genes (CD44, MMP9 and CHI3L1). Our findings suggest that phospho-c-Jun activates an important regulatory mechanism to control DNMT1 expression and regulate global DNA methylation in Glioblastoma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Proteínas Proto-Oncogénicas c-jun / Metilación de ADN / ADN (Citosina-5-)-Metiltransferasa 1 / Glioma Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Oncotarget Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Proteínas Proto-Oncogénicas c-jun / Metilación de ADN / ADN (Citosina-5-)-Metiltransferasa 1 / Glioma Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Oncotarget Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos