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

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Disclosure

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

    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 & Hisahiro Matsubara MD, PhD

  2. Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Takayoshi Suzuki PhD

Authors
  1. Isamu Hoshino MD, PhD
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  2. Yasunori Akutsu MD, PhD
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  14. Hisahiro Matsubara MD, PhD
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Corresponding author

Correspondence to Isamu Hoshino MD, PhD.

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Hoshino, I., Akutsu, Y., Murakami, K. et al. Histone Demethylase LSD1 Inhibitors Prevent Cell Growth by Regulating Gene Expression in Esophageal Squamous Cell Carcinoma Cells. Ann Surg Oncol 23, 312–320 (2016). https://doi.org/10.1245/s10434-015-4488-1

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  • DOI: https://doi.org/10.1245/s10434-015-4488-1

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