Hoshino Isamu, Takahashi Masahiko, Akutsu Yasunori, Murakami Kentaro, Matsumoto Yasunori, Suito Hiroshi, Sekino Nobufumi, Komatsu Aki, Iida Keiko, Suzuki Takayoshi, Inoue Itsuro, Ishige Fumitaka, Iwatate Yosuke, Matsubara Hisahiro
Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
Division of Gastroenterological Surgery, Chiba Cancer Center, Chuo-ku, Chiba 260-8717, Japan.
Oncol Lett. 2019 Jul;18(1):872-881. doi: 10.3892/ol.2019.10350. Epub 2019 May 13.
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.
基因表达受组蛋白修饰、组蛋白乙酰化和甲基化调控,但在肿瘤发生和癌症发展过程中已观察到这些修饰的异常。赖氨酸特异性组蛋白去甲基化酶1(LSD1)抑制剂作为一种组蛋白去甲基化酶,其作用被认为是通过控制基因表达来实现的。本研究的目的是利用染色质免疫沉淀(ChIP)-Seq技术阐明LSD1抑制剂对食管癌细胞系基因表达的影响。通过微阵列分析,明确了LSD1抑制剂NCL1诱导食管鳞状细胞癌(ESCC)细胞系基因表达变化的综合分析。此外,使用SimpleChIP plus Enzymatic Chromatin IP试剂盒进行ChIP-seq分析。NCL1强烈抑制ESCC细胞系T.Tn和TE2细胞的增殖,并进一步诱导细胞凋亡。根据ChIP-seq和微阵列的联合分析,在两个细胞系中,17个基因上调,16个基因下调。本研究中进行的综合基因表达研究被认为有助于分析LSD1抑制剂对ESCC患者抗肿瘤作用的机制。