title: Histone Demethylase LSD1 Inhibitors Prevent Cell Growth by Regulating Gene Expression in Esophageal Squamous Cell Carcinoma Cells.
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.
authors: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. i_hosino@chiba-u.jp.
authors: Isamu
authors: I
authors: Hoshino
authors: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Yasunori
authors: Y
authors: Akutsu
authors: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Kentaro
authors: K
authors: Murakami
authors: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Naoki
authors: N
authors: Akanuma
authors: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Yuka
authors: Y
authors: Isozaki
authors: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Tetsuro
authors: T
authors: Maruyama
authors: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Takeshi
authors: T
authors: Toyozumi
authors: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Yasunori
authors: Y
authors: Matsumoto
authors: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Hiroshi
authors: H
authors: Suito
authors: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Masahiko
authors: M
authors: Takahashi
authors: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Nobufumi
authors: N
authors: Sekino
authors: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Aki
authors: A
authors: Komatsu
authors: Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Takayoshi
authors: T
authors: Suzuki
authors: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors: Hisahiro
authors: H
authors: Matsubara
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D056572:Histone Deacetylase Inhibitors; D012333:RNA, Messenger; D056466:Histone Demethylases; C495195:KDM1A protein, human