Document Type

Article

Publication Date

5-1-2019

Publication Title

Epigenomics

Keywords

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

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 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.

Clinical Institute

Cancer

Department

Oncology

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