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c-Jun-N-terminal ph...
c-Jun-N-terminal phosphorylation regulates DNMT1 expression and genome wide methylation in gliomas
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- Heiland, Dieter H. (author)
- Univ Freiburg, Med Ctr, Dept Neurosurg, Freiburg, Germany.;Univ Freiburg, Fac Med, Freiburg, Germany.
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- Ferrarese, Roberto (author)
- Univ Freiburg, Med Ctr, Dept Neurosurg, Freiburg, Germany.;Univ Freiburg, Fac Med, Freiburg, Germany.
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- Claus, Rainer (author)
- Univ Freiburg, Med Ctr, Dept Hematol Oncol & Stem Cell Transplantat, Freiburg, Germany.
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- Dai, Fangping (author)
- Univ Freiburg, Med Ctr, Dept Neurosurg, Freiburg, Germany.;Univ Freiburg, Fac Med, Freiburg, Germany.
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- Masilamani, Anie P. (author)
- Univ Freiburg, Med Ctr, Dept Neurosurg, Freiburg, Germany.;Univ Freiburg, Fac Med, Freiburg, Germany.
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- Kling, Eva (author)
- Univ Freiburg, Med Ctr, Dept Neurosurg, Freiburg, Germany.;Univ Freiburg, Fac Med, Freiburg, Germany.
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- Weyerbrock, Astrid (author)
- Univ Freiburg, Med Ctr, Dept Neurosurg, Freiburg, Germany.;Univ Freiburg, Fac Med, Freiburg, Germany.
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- Kling, Teresia (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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- Nelander, Sven (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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- Carro, Maria S. (author)
- Univ Freiburg, Med Ctr, Dept Neurosurg, Freiburg, Germany.;Univ Freiburg, Fac Med, Freiburg, Germany.
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Univ Freiburg, Med Ctr, Dept Neurosurg, Freiburg, Germany;Univ Freiburg, Fac Med, Freiburg, Germany. Univ Freiburg, Med Ctr, Dept Hematol Oncol & Stem Cell Transplantat, Freiburg, Germany. (creator_code:org_t)
- 2016-12-28
- 2017
- English.
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:4, s. 6940-6954
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http://www.oncotarge...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Glioblastoma
- G-CIMP
- DNMT1
- p-c-Jun
- mesenchymal
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- ref (subject category)
- art (subject category)
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Heiland, Dieter ...
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Ferrarese, Rober ...
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Claus, Rainer
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Dai, Fangping
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Masilamani, Anie ...
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Kling, Eva
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Weyerbrock, Astr ...
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Kling, Teresia
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Nelander, Sven
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Carro, Maria S.
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Uppsala University