دورية أكاديمية
c-Jun-N-terminal phosphorylation regulates DNMT1 expression and genome wide methylation in gliomas.
| العنوان: | c-Jun-N-terminal phosphorylation regulates DNMT1 expression and genome wide methylation in gliomas. |
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| المؤلفون: | Heiland DH; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Ferrarese R; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Claus R; Department of Hematology, Oncology, and Stem Cell Transplantation, University of Freiburg Medical Center, Freiburg, Germany., Dai F; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Masilamani AP; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Kling E; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Weyerbrock A; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Kling T; Department of Immunology, Genetics and Pathology and Science for Life Laboratories, University of Uppsala, Uppsala, Sweden., Nelander S; Department of Immunology, Genetics and Pathology and Science for Life Laboratories, University of Uppsala, Uppsala, Sweden., Carro MS; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany. |
| المصدر: | Oncotarget [Oncotarget] 2017 Jan 24; Vol. 8 (4), pp. 6940-6954. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Impact Journals Country of Publication: United States NLM ID: 101532965 Publication Model: Print Cited Medium: Internet ISSN: 1949-2553 (Electronic) Linking ISSN: 19492553 NLM ISO Abbreviation: Oncotarget Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Albany, N.Y. : Impact Journals |
| مواضيع طبية MeSH: | DNA Methylation*/drug effects, Brain Neoplasms/*metabolism , DNA (Cytosine-5-)-Methyltransferase 1/*genetics , Glioma/*metabolism , Proto-Oncogene Proteins c-jun/*metabolism, Anisomycin/pharmacology ; Brain Neoplasms/genetics ; Cell Line, Tumor ; DNA (Cytosine-5-)-Methyltransferase 1/metabolism ; Epigenesis, Genetic/drug effects ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Genome, Human ; Glioma/genetics ; Humans ; Phosphorylation ; Prognosis ; Promoter Regions, Genetic/drug effects ; Survival Analysis ; Up-Regulation/drug effects |
| مستخلص: | 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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| فهرسة مساهمة: | Keywords: DNMT1; G-CIMP; Glioblastoma; mesenchymal; p-c-Jun |
| المشرفين على المادة: | 0 (Proto-Oncogene Proteins c-jun) 6C74YM2NGI (Anisomycin) EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1) EC 2.1.1.37 (DNMT1 protein, human) |
| تواريخ الأحداث: | Date Created: 20161231 Date Completed: 20180222 Latest Revision: 20211109 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC5351681 |
| DOI: | 10.18632/oncotarget.14330 |
| PMID: | 28036297 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1949-2553 |
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| DOI: | 10.18632/oncotarget.14330 |