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

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.

JmjC-KDMs KDM3A and KDM6B modulate radioresistance under hypoxic conditions in esophageal squamous cell carcinoma

“…Importantly, both in vitro and in vivo experiments support the demethylating role of KDM3A as a mediator of radioresistance, since higher H3K9me2 levels were observed in IOX1 treated tumors. Interestingly, deregulation of JmjC-KDMs, including LSD1 48 , KDM3C 49 , KDM4C 50 , KDM7B 46 , and UTX/KDM6A 51 , has been implicated in esophageal carcinogenesis, although published data concerning KDM3A and KDM6B is notoriously lacking. Indeed, our study is the first to demonstrate that, in primary ESCC, KDM3A overexpression positively associates with the hypoxic markers, HIF-1α and CAIX, further supporting the in vitro data 40 .…”

LSD1/KDM1A inhibitors in clinical trials: advances and prospects

“…Pharmacological inhibition of LSD1 leads to inhibition of proliferation, differentiation, invasion, and migration in vitro and in vivo [26]. The combinatory analysis of chromatin immunoprecipitation (ChIP)-Seq and microarray revealed the genes affected by LSD1 inhibition in esophageal squamous cell carcinoma (ESCC) cells [27], in which 17 genes were upregulated and 16 genes were downregulated. In addition to the demethylase activity of LSD1, its demethylase-independent activity is also implicated during carcinogenesis [28–31], this finding may explain the ineffectiveness of catalytic inhibition of LSD1 in some cancers [32, 33].…”

The Choice of Candidates in Survival Markers Based on Coordinated Gene Expression in Renal Cancer

“…Although increased expression of BHLHE41 stimulates the proliferation of tumor cells, which is especially important for tumor growth at the initial stage of development, it also inhibits its further development. In the further stages, cell invasion and EMT are inhibited by BHLHE41 ( 63 ), lending to this gene’s classification as a tumor suppressor ( 64 ). Suppression of EMT and metastasis by BHLHE41 has been observed in breast ( 65 – 67 ), endometrial, and pancreatic cancer ( 63 , 68 ).…”