ChIP-seq analysis reveals alteration of H3K4 trimethylation occupancy in cancer-related genes by cold atmospheric plasma.

Cold atmospheric plasma (CAP) has gained attention for use in cancer treatment owing to its ability to preferentially induce cancer cell death; however, the involved molecular mechanism remains to be elucidated. Herein, an epigenetic effect of CAP on cancer cells was examined by performing a genome-wide ChIP-seq for H3K4me3 in MCF-7 breast cancer cell line. Consequently, 899 genes showed significantly changed methylation level at H3K4 with constructing "Cellular Compromise, DNA Replication, Recombination, Repair, and Cell Cycle" as the top network. Comparisons with expression array data revealed a coincidence between histone modification and gene expression for 18 genes, and the association was confirmed by ChIP-PCR and qRT-PCR for selected genes. The expression of the affected genes, such as HSCB and PRPS1, was recovered when a histone demethylase JARID1A was inhibited. Furthermore, JARID1A was induced by CAP via the reactive oxygen species signaling. The two genes are known as oncogenes and show a higher expression in breast cancer tissue, and this was supported by the decreased colony formation ability of MCF-7 cells when the cells were treated with siRNAs against each gene. Taken together, these data indicate that CAP inhibits cancer cell proliferation by modulating the methylation level of H3K4 corresponding to oncogenes.