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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 1/2016

01-01-2016 | Translational Research and Biomarkers

Histone Demethylase LSD1 Inhibitors Prevent Cell Growth by Regulating Gene Expression in Esophageal Squamous Cell Carcinoma Cells

Authors: Isamu Hoshino, MD, PhD, Yasunori Akutsu, MD, PhD, Kentaro Murakami, MD, PhD, Naoki Akanuma, MD, PhD, Yuka Isozaki, MD, PhD, Tetsuro Maruyama, MD, PhD, Takeshi Toyozumi, MD, PhD, Yasunori Matsumoto, MD, Hiroshi Suito, MD, Masahiko Takahashi, MD, Nobufumi Sekino, MD, Aki Komatsu, PhD, Takayoshi Suzuki, PhD, Hisahiro Matsubara, MD, PhD

Published in: Annals of Surgical Oncology | Issue 1/2016

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Abstract

Background

The expression of genes can be influenced by the balance of histone acetylation and/or histone demethylation, with an imbalance of these processes possibly observed in many cancers. The histone demethylase LSD1 inhibitor activity is associated with selective transcriptional regulation and alterations in the gene expression. However, the exact mechanisms underlying the antitumor effects of LSD1 inhibitors are not fully understood.

Methods

The antitumor effects of NCL1, an LSD1 inhibitor, in esophageal squamous cell cancer (ESCC) cell lines were evaluated. A comprehensive analysis of the changes in the gene expression in ESCC cell lines induced by NCL1 was carried out using a microarray analysis. A loss-of-function assay using a siRNA analysis was performed to examine the oncogenic function of the gene.

Results

NCL1 strongly inhibited the cell growth of T.Tn and TE2 ESCC cells and induced apoptosis. According to the microarray analysis, 81 genes in the T.Tn cells and 149 genes in the TE2 cells were up- or down-regulated 2-fold or more by NCL1 exposure. Among these genes, 27 were contained in both cell lines and exhibited similar expression patterns. PHLDB2, one of the genes down-regulated by NCL1, was overexpressed in the ESCC tumor tissues. Moreover, a high expression level of PHLDB2 was found to be significantly correlated with poor prognosis.

Conclusions

The present observations of the comprehensive analysis of the gene expression levels provide insight into the mechanisms underlying the antitumor effects of LSD1 inhibitors in ESCC patients.
Appendix
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Metadata
Title
Histone Demethylase LSD1 Inhibitors Prevent Cell Growth by Regulating Gene Expression in Esophageal Squamous Cell Carcinoma Cells
Authors
Isamu Hoshino, MD, PhD
Yasunori Akutsu, MD, PhD
Kentaro Murakami, MD, PhD
Naoki Akanuma, MD, PhD
Yuka Isozaki, MD, PhD
Tetsuro Maruyama, MD, PhD
Takeshi Toyozumi, MD, PhD
Yasunori Matsumoto, MD
Hiroshi Suito, MD
Masahiko Takahashi, MD
Nobufumi Sekino, MD
Aki Komatsu, PhD
Takayoshi Suzuki, PhD
Hisahiro Matsubara, MD, PhD
Publication date
01-01-2016
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 1/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4488-1

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