Dataset Information

Prognostic relevance of miRNA-155 methylation in anaplastic glioma.

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)?B activation.Preconditioning glioma cells with an NF?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?B inhibition may provide treatment options with a special focus on patients with IDH wild type tumors.

SUBMITTER: Schliesser MG

PROVIDER: S-EPMC5347671 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Prognostic relevance of miRNA-155 methylation in anaplastic glioma.

Schliesser Maximilian Georg MG Claus Rainer R Hielscher Thomas T Grimm Christiane C Weichenhan Dieter D Blaes Jonas J Wiestler Benedikt B Hau Peter P Schramm Johannes J Sahm Felix F Weiß Elisa K EK Weiler Markus M Baer Constance C Schmidt-Graf Friederike F Schackert Gabriele G Westphal Manfred M Hertenstein Anne A Roth Patrick P Galldiks Norbert N Hartmann Christian C Pietsch Torsten T Felsberg Joerg J Reifenberger Guido G Sabel Michael Christoph MC Winkler Frank F von Deimling Andreas A Meisner Christoph C Vajkoczy Peter P Platten Michael M Weller Michael M Plass Christoph C Wick Wolfgang W

Oncotarget 20161201 50

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 f ...[more]

PMID: 27880937

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Project description:This study evaluated differences in the clinical appearance of patients with hepatocellular carcinoma (HCC) based on plasma level and regulation of microRNAs (miRNA-29c, miRNA-21, and miRNA-155). The observational-analytical study with a cross-sectional design was conducted on 36 HCC patients and 36 healthy controls. The blood samples were collected from 2 Province Hospitals (Dr. Sardjito Hospital and Prof. Dr. Margono Soekarjo Hospital) for HCC and the Blood Bank Donor of the Indonesian Red Cross for 36 healthy controls. These blood samples were treated as follows: plasma isolation, RNA isolation, cDNA synthesis, quantification by qRT-PCR using a sequence-specific forward primer, and normalization of miRNA using housekeeping-stably miRNA-16. There were only 27 HCC patients with complete clinical variables (neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), platelet count, albumin, C-reactive protein (CRP), and cholinesterase (ChE)) that were able to analyses for regulation miRNAs based on its fold change expression miRNA target. All 27 HCC subjects were follow-up until 3-years of monitoring for their overall survival. The miRNA plasma expression was analyzed by Bio-Rad CFX 96 Manager software to determine the cycle of quantification, followed by the calculation of expression levels using Livak's methods. Data were analyzed using STATA 11.0, with a significant value of p<0.05. The miRNAs expression of HCC subjects were lower than that healthy control subjects in miRNA-29c (down-regulation 1.83-fold), higher than that healthy control subjects in miRNA 21 and miRNA-155 (up-regulation, 1.74-fold; 1.55-fold) respectively. NLR, CRP, ChE, and platelet count showed a significant difference in miRNA-29c regulation, though neutrophil count showed a significant difference in miRNA-21 and miRNA-155 regulation (p<0.05). Conclusion: Plasma biomarkers: miRNA-21 and miRNA-155 might be potential biomarkers as onco-miR in HCC subjects, while miRNA-29c might act as a tumor suppressor. Significant evidence was identified with clinical progression based on the regulation of miRNAs, which was consistent with miRNA -29c.

Dataset Information

Prognostic relevance of miRNA-155 methylation in anaplastic glioma.

Publications

Prognostic relevance of miRNA-155 methylation in anaplastic glioma.

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