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

Authors :
Hoshino I
Akutsu Y
Murakami K
Akanuma N
Isozaki Y
Maruyama T
Toyozumi T
Matsumoto Y
Suito H
Takahashi M
Sekino N
Komatsu A
Suzuki T
Matsubara H
Source :
Annals of surgical oncology [Ann Surg Oncol] 2016 Jan; Vol. 23 (1), pp. 312-20. Date of Electronic Publication: 2015 Mar 20.
Publication Year :
2016

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.<br />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.<br />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.<br />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.

Details

Language :
English
ISSN :
1534-4681
Volume :
23
Issue :
1
Database :
MEDLINE
Journal :
Annals of surgical oncology
Publication Type :
Academic Journal
Accession number :
25791791
Full Text :
https://doi.org/10.1245/s10434-015-4488-1