Schliesser, Maximilian Georg and Claus, Rainer and Hielscher, Thomas and Grimm, Christiane and Weichenhan, Dieter and Blaes, Jonas and Wiestler, Benedikt and Hau, Peter and Schramm, Johannes and Sahm, Felix and Weiss, Elisa K. and Weiler, Markus and Baer, Constance and Schmidt-Graf, Friederike and Schackert, Gabriele and Westphal, Manfred and Hertenstein, Anne and Roth, Patrick and Galldiks, Norbert and Hartmann, Christian and Pietsch, Torsten and Felsberg, Joerg and Reifenberger, Guido and Sabel, Michael Christoph and Winkler, Frank and von Deimling, Andreas and Meisner, Christoph and Vajkoczy, Peter and Platten, Michael and Weller, Michael and Plass, Christoph and Wick, Wolfgang (2016) Prognostic relevance of miRNA-155 methylation in anaplastic glioma. ONCOTARGET, 7 (50). pp. 82028-82045. ISSN 1949-2553,
Full text not available from this repository. (Request a copy)Abstract
The outcome of patients with anaplastic gliomas varies considerably depending on single molecular markers, such as mutations of the isocitrate dehydrogenase (IDH) genes, as well as molecular classifications based on epigenetic or genetic profiles. Remarkably, 98% of the RNA within a cell is not translated into proteins. Of those, especially microRNAs (miRNAs) have been shown not only to have a major influence on physiologic processes but also to be deregulated and prognostic in malignancies. To find novel survival markers and treatment options we performed unbiased DNA methylation screens that revealed 12 putative miRNA promoter regions with differential DNA methylation in anaplastic gliomas. Methylation of these candidate regions was validated in different independent patient cohorts revealing a set of miRNA promoter regions with prognostic relevance across data sets. Of those, miR-155 promoter methylation and miR-155 expression were negatively correlated and especially the methylation showed superior correlation with patient survival compared to established biomarkers. Functional examinations in malignant glioma cells further cemented the relevance of miR-155 for tumor cell viability with transient and stable modifications indicating an onco-miRNA activity. MiR-155 also conferred resistance towards alkylating temozolomide and radiotherapy as consequence of nuclear factor (NF)kappa B activation. Preconditioning glioma cells with an NF kappa B inhibitor reduced therapy resistance of miR-155 overexpressing cells. These cells resembled tumors with a low methylation of the miR-155 promoter and thus mir-155 or NF kappa B inhibition may provide treatment options with a special focus on patients with IDH wild type tumors.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHRONIC LYMPHOCYTIC-LEUKEMIA; VIRUS-INDUCED LYMPHOMAS; DNA METHYLATION; CELLS; IDENTIFICATION; GLIOBLASTOMA; LANDSCAPE; MIR-155; GENOME; EXPRESSION; anaplastic glioma; miR-155; IDH; NF kappa B; NOA-04 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Apr 2019 14:02 |
| Last Modified: | 08 Apr 2019 14:02 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3786 |
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