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

Annals of Surgical Oncology
Isamu HoshinoHisahiro Matsubara

Abstract

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. 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. 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. Mor...Continue Reading

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Citations

Jan 5, 2017·Cold Spring Harbor Perspectives in Medicine·Ashwini JambhekarYang Shi
Oct 3, 2018·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Yosuke Ota, Takayoshi Suzuki
Jan 31, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Wubin DingTieliu Shi
May 8, 2020·Expert Opinion on Therapeutic Targets·Shaun Egolf, Brian C Capell
May 21, 2020·International Journal of Molecular Sciences·Nair LopesCarmen Jerónimo
Feb 16, 2019·Nature Reviews. Urology·Sina JostesHubert Schorle
Dec 15, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Yang LiGuojun Zhang

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