Commonly integrated epigenetic modifications of differentially expressed genes lead to adaptive resistance in cancer
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(Published version)
Date
2019
Authors
Al Emran, A.
Marzese, D.M.
Menon, D.R.
Hammerlindl, H.
Ahmed, F.
Richtig, E.
Duijf, P.
Hoon, D.S.B.
Schaider, H.
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Journal article
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Epigenomics, 2019; 11(7):723-737
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Abstract
Aim: To investigate the integrated epigenetic regulation of acquired drug resistance in cancer.
Materials & methods: Our gene expression data of five induced drug-tolerant cell models, one resistant cell line and one publicly available drug-resistant dataset were integrated to identify common differentially expressed genes and pathways. ChIP-seq and DNA methylation by HM450K beadchip were used to study the epigenetic profile of differential expressed genes.
Results & conclusion: Integrated transcriptomic analysis identified a common ‘viral mimicry’ related gene signature in induced drug-tolerant cells and the resistant state. Analysis of the epigenetic regulation revealed a common set of downregulated genes, which are marked and regulated by a concomitant loss of H3K4me3, gain of H3K9me3 and increment of regional DNA methylation levels associated with tumor suppressor genes and apoptotic signaling.
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Data source: Supplementary data, http://www.futuremedicine.com/doi/full/10.2217/epi-2018-0173
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Copyright 2019 Helmut Schaider. This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/4.0/)