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000130493 1001_ $$0P:(DE-He78)2970cb1f38e9cb41d755455acd14893e$$aSchliesser, Maximilian$$b0$$eFirst author$$udkfz
000130493 245__ $$aPrognostic relevance of miRNA-155 methylation in anaplastic glioma.
000130493 260__ $$a[S.l.]$$bImpact Journals LLC$$c2016
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000130493 520__ $$aThe 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)κB activation.Preconditioning glioma cells with an NFκB 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 NFκB inhibition may provide treatment options with a special focus on patients with IDH wild type tumors.
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000130493 7001_ $$0P:(DE-HGF)0$$aClaus, Rainer$$b1
000130493 7001_ $$0P:(DE-He78)743a4a82daab55306a2c88b9f6bf8c2f$$aHielscher, Thomas$$b2$$udkfz
000130493 7001_ $$0P:(DE-HGF)0$$aGrimm, Christiane$$b3
000130493 7001_ $$0P:(DE-He78)ff4024f7bc236e7897d9c18ee19c451f$$aWeichenhan, Dieter$$b4$$udkfz
000130493 7001_ $$0P:(DE-He78)e9a2788d72412f2864cee1ff0cd6b3ca$$aBlaes, Jonas$$b5$$udkfz
000130493 7001_ $$0P:(DE-He78)2d0c564eca775a62ff86225f7717af12$$aWiestler, Benedikt Paul Otmar$$b6$$udkfz
000130493 7001_ $$0P:(DE-HGF)0$$aHau, Peter$$b7
000130493 7001_ $$aSchramm, Johannes$$b8
000130493 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b9$$udkfz
000130493 7001_ $$0P:(DE-HGF)0$$aWeiß, Elisa K$$b10
000130493 7001_ $$aWeiler, Markus$$b11
000130493 7001_ $$aBaer, Constance$$b12
000130493 7001_ $$aSchmidt-Graf, Friederike$$b13
000130493 7001_ $$aSchackert, Gabriele$$b14
000130493 7001_ $$aWestphal, Manfred$$b15
000130493 7001_ $$0P:(DE-He78)82e0de3d5aa5330bb2470e74c48773ca$$aHertenstein, Anne$$b16$$udkfz
000130493 7001_ $$aRoth, Patrick$$b17
000130493 7001_ $$aGalldiks, Norbert$$b18
000130493 7001_ $$aHartmann, Christian$$b19
000130493 7001_ $$aPietsch, Torsten$$b20
000130493 7001_ $$aFelsberg, Joerg$$b21
000130493 7001_ $$aReifenberger, Guido$$b22
000130493 7001_ $$aSabel, Michael Christoph$$b23
000130493 7001_ $$0P:(DE-He78)6c294453ee36ad59deddc5494fa6aa4b$$aWinkler, Frank$$b24$$udkfz
000130493 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b25$$udkfz
000130493 7001_ $$aMeisner, Christoph$$b26
000130493 7001_ $$aVajkoczy, Peter$$b27
000130493 7001_ $$0P:(DE-He78)5ef8651b0f857b9c640aa5b1498c43b5$$aPlatten, Michael$$b28$$udkfz
000130493 7001_ $$aWeller, Michael$$b29
000130493 7001_ $$0P:(DE-He78)4301875630bc997edf491c694ae1f8a9$$aPlass, Christoph$$b30$$udkfz
000130493 7001_ $$0P:(DE-He78)92e9783ca7025f36ce14e12cd348d2ee$$aWick, Wolfgang$$b31$$eLast author$$udkfz
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000130493 9201_ $$0I:(DE-He78)G160-20160331$$kG160$$lNeuroimmunologie und Hirntumorimmunologie$$x0
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