Commonly Integrated Epigenetic Modifications of Differentially Expressed Genes Lead to Adaptive Resistance in Cancer

Abstract

<b>Aim:</b> To investigate the integrated epigenetic regulation of acquired drug resistance in cancer. <b>Materials & methods:</b> 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. <b>Results & conclusion:</b> 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.