Schliesser, Maximilian Georg, Claus, Rainer ORCID: 0000-0003-2617-8766, Hielscher, Thomas, Grimm, Christiane, Weichenhan, Dieter, Blaes, Jonas, Wiestler, Benedikt, Hau, Peter ORCID: 0000-0003-3894-5053, Schramm, Johannes, Sahm, Felix ORCID: 0000-0001-5441-1962, Weiss, Elisa K., Weiler, Markus, Baer, Constance, Schmidt-Graf, Friederike, Schackert, Gabriele, Westphal, Manfred, Hertenstein, Anne, Roth, Patrick ORCID: 0000-0003-3897-214X, Galldiks, Norbert ORCID: 0000-0002-2485-1796, Hartmann, Christian, Pietsch, Torsten, Felsberg, Joerg, Reifenberger, Guido, Sabel, Michael Christoph, Winkler, Frank, von Deimling, Andreas ORCID: 0000-0002-5863-540X, Meisner, Christoph, Vajkoczy, Peter, Platten, Michael ORCID: 0000-0002-4746-887X, Weller, Michael ORCID: 0000-0002-1748-174X, Plass, Christoph and Wick, Wolfgang ORCID: 0000-0002-6171-634X (2016). Prognostic relevance of miRNA-155 methylation in anaplastic glioma. Oncotarget, 7 (50). S. 82028 - 82046. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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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: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schliesser, Maximilian GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Claus, RainerUNSPECIFIEDorcid.org/0000-0003-2617-8766UNSPECIFIED
Hielscher, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grimm, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weichenhan, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blaes, JonasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiestler, BenediktUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hau, PeterUNSPECIFIEDorcid.org/0000-0003-3894-5053UNSPECIFIED
Schramm, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sahm, FelixUNSPECIFIEDorcid.org/0000-0001-5441-1962UNSPECIFIED
Weiss, Elisa K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weiler, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baer, ConstanceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt-Graf, FriederikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schackert, GabrieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Westphal, ManfredUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hertenstein, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roth, PatrickUNSPECIFIEDorcid.org/0000-0003-3897-214XUNSPECIFIED
Galldiks, NorbertUNSPECIFIEDorcid.org/0000-0002-2485-1796UNSPECIFIED
Hartmann, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pietsch, TorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Felsberg, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reifenberger, GuidoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sabel, Michael ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winkler, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Deimling, AndreasUNSPECIFIEDorcid.org/0000-0002-5863-540XUNSPECIFIED
Meisner, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vajkoczy, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Platten, MichaelUNSPECIFIEDorcid.org/0000-0002-4746-887XUNSPECIFIED
Weller, MichaelUNSPECIFIEDorcid.org/0000-0002-1748-174XUNSPECIFIED
Plass, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wick, WolfgangUNSPECIFIEDorcid.org/0000-0002-6171-634XUNSPECIFIED
URN: urn:nbn:de:hbz:38-252580
DOI: 10.18632/oncotarget.13452
Journal or Publication Title: Oncotarget
Volume: 7
Number: 50
Page Range: S. 82028 - 82046
Date: 2016
Publisher: IMPACT JOURNALS LLC
Place of Publication: ORCHARD PARK
ISSN: 1949-2553
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
VIRUS-INDUCED LYMPHOMAS; DNA METHYLATION; IDENTIFICATION; LANDSCAPE; MIR-155; CELL; EXPRESSION; MICRORNAS; GENOME; CHEMOSENSITIVITYMultiple languages
Oncology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/25258

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