Cell Line, Tumor; DNA Methylation; Down-Regulation; Drug Resistance, Neoplasm; Drug Tolerance; Gene Expression Profiling; Histones; Humans; Insulin-Like Growth Factor Binding Protein 5; Neoplasms; Promoter Regions, Genetic; Survival Analysis
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 down-regulated 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.
Emran, Abdullah Al; Marzese, Diego M; Menon, Dinoop R; Hammerlindl, Heinz; Ahmed, Farzana; Richtig, Erika; Duijf, Pascal; Hoon, Dave; and Schaider, Helmut, "Commonly integrated epigenetic modifications of differentially expressed genes lead to adaptive resistance in cancer." (2019). Articles, Abstracts, and Reports. 3269.