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Methylation deregulation of miRNA promoters identifies miR124-2 as a survival biomarker in Breast Cancer in very young women

Title: Methylation deregulation of miRNA promoters identifies miR124-2 as a survival biomarker in Breast Cancer in very young women
Authors: Oltra, SS
Pena-Chilet, M
Vidal-Tomas, V
Flower, K
Teresa Martinez, M
Alonso, E
Burgues, O
Lluch, A
Flanagan, JM
Ribas, G
Item Type: Journal Article
Abstract: MiRNAs are part of the epigenetic machinery, and are also epigenetically modified by DNA methylation. MiRNAs regulate expression of different genes, so any alteration in their methylation status may affect their expression. We aimed to identify methylation differences in miRNA encoding genes in breast cancer affecting women under 35 years old (BCVY), in order to identify potential biomarkers in these patients. In Illumina Infinium MethylationEPIC BeadChip samples (metEPICVal), we analysed the methylation of 9,961 CpG site regulators of miRNA-encoding genes present in the array. We identified 193 differentially methylated CpG sites in BCVY (p-value < 0.05 and methylation differences ±0.1) that regulated 83 unique miRNA encoding genes. We validated 10 CpG sites using two independent datasets based on Infinium Human Methylation 450k array. We tested gene expression of miRNAs with differential methylation in BCVY in a meta-analysis using The Cancer Genome Atlas (TCGA), Clariom D and Affymetrix datasets. Five miRNAs (miR-9, miR-124-2, miR-184, miR-551b and miR-196a-1) were differently expressed (FDR p-value < 0.01). Finally, only miR-124-2 shows a significantly different gene expression by quantitative real-time PCR. MiR-124-hypomethylation presents significantly better survival rates for older patients as opposed to the worse prognosis observed in BCVY, identifying it as a potential specific survival biomarker in BCVY.
Issue Date: 26-Sep-2018
Date of Acceptance: 2-Aug-2018
URI: http://hdl.handle.net/10044/1/63756
DOI: https://dx.doi.org/10.1038/s41598-018-32393-3
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 8
Issue: 1
Copyright Statement: © 2018 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
Publication Status: Published
Article Number: 14373
Online Publication Date: 2018-09-26
Appears in Collections:Department of Surgery and Cancer