Genome-wide ChIP-seq data with a transcriptome analysis reveals the groups of genes regulated by histone demethylase LSD1 inhibition in esophageal squamous cell carcinoma cells

Isamu Hoshino; Masahiko Takahashi; Yasunori Akutsu; Kentaro Murakami; Yasunori Matsumoto; Hiroshi Suito; Nobufumi Sekino; Aki Komatsu; Keiko Iida; Takayoshi Suzuki; Itsuro Inoue; Fumitaka Ishige; Yosuke Iwatate; Hisahiro Matsubara

doi:10.3892/ol.2019.10350

Genome-wide ChIP-seq data with a transcriptome analysis reveals the groups of genes regulated by histone demethylase LSD1 inhibition in esophageal squamous cell carcinoma cells

Oncol Lett. 2019 Jul;18(1):872-881. doi: 10.3892/ol.2019.10350. Epub 2019 May 13.

Authors

Affiliations

¹ Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
² Division of Gastroenterological Surgery, Chiba Cancer Center, Chuo-ku, Chiba 260-8717, Japan.
³ Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kita-ku, Kyoto 403-8334, Japan.
⁴ Division of Human Genetics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
⁵ Department of Hepatobiliary and Pancreatic Surgery, Chiba Cancer Center, Chuo-ku, Chiba 260-8717, Japan.

Abstract

Expression of genes is controlled by histone modification, histone acetylation and methylation, but abnormalities of these modifications have been observed in carcinogenesis and cancer development. The effect of the lysine-specific histone demethylase 1 (LSD1) inhibitor, a demethylating enzyme of histones, is thought to be caused by controlling the expression of genes. The aim of the present study is to elucidate the efficacies of the LSD1 inhibitor on the gene expression of esophageal cancer cell lines using chromatin immunoprecipitation (ChIP)-Seq. A comprehensive analysis of gene expression changes in esophageal squamous cell carcinoma (ESCC) cell lines induced by the LSD1 inhibitor NCL1 was clarified via analysis using microarray. In addition, ChIP-seq analysis was conducted using a SimpleChIP plus Enzymatic Chromatin IP kit. NCL1 strongly suppressed the proliferation of T.Tn and TE2 cells, which are ESCC cell lines, and further induced apoptosis. According to the combinatory analysis of ChIP-seq and microarray, 17 genes were upregulated, and 16 genes were downregulated in both cell lines. The comprehensive gene expression study performed in the present study is considered to be useful for analyzing the mechanism of the antitumor effect of the LSD1 inhibitor in patients with ESCC.

Keywords: chromatin immunoprecipitation-seq; esophageal squamous cell carcinoma; histone demethylase inhibitor; lysine-specific histone demethylase 1; lysine-specific histone demethylase 1 inhibitor.