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Regulation of tissue factor pathway inhibitor-2 (TFPI-2) expression by lysine-specific demethylase 1 and 2 (LSD1 and LSD2).

Authors
  • Mino, Koshiki
  • Nishimura, Satoshi
  • Ninomiya, Shogo
  • Tujii, Hiroshi
  • Matsumori, Yasumasa
  • Tsuchida, Mie
  • Hosoi, Miho
  • Koseki, Koichi
  • Wada, Shuichi
  • Hasegawa, Makoto
  • Sasaki, Ryuzo
  • Murakami-Yamaguchi, Yukie
  • Narita, Hiroshi
  • Suzuki, Takayoshi
  • Miyata, Naoki
  • Mizukami, Tamio
Type
Published Article
Journal
Bioscience Biotechnology and Biochemistry
Publisher
Informa UK (Taylor & Francis)
Publication Date
Jan 01, 2014
Volume
78
Issue
6
Pages
1010–1017
Identifiers
DOI: 10.1080/09168451.2014.910104
PMID: 25036127
Source
Medline
Keywords
License
Unknown

Abstract

Tissue factor pathway inhibitor-2 (TFPI-2) is a major inhibitor of extracellular matrix degradation. Decreases in TFPI-2 contribute to malignant tumor cell production, and TFPI-2 is a presumed tumor suppressor. TFPI-2 gene transcription is regulated by two epigenetic mechanisms: DNA methylation of the promoter and K4 methylation of histone 3 (H3). Lysine-specific demethylase 1 (LSD1) and LSD2 demethylate H3K4me2/1. LSD1 has been implicated in TFPI-2 regulation through both epigenetic mechanisms, but the involvement of LSD2 remains unknown. We prepared a monoclonal anti-LSD2 antibody that clearly distinguishes LSD2 from LSD1. Knockdown of LSD1 or LSD2 by siRNAs increased TFPI-2 protein and mRNA. Simultaneous knockdown of both LSD1 and LSD2 showed additive effects. Bisulfite sequencing revealed that CpG sites in the TFPI-2 promoter region were unmethylated. These results indicate that LSD2 also contributes to TFPI-2 regulation through histone modification, and that further studies of the involvement of LSD2 in tumor malignancy are warranted.

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