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

Koshiki Mino1, Satoshi Nishimura, Shogo Ninomiya

  • 1a Graduate School of Bio-Science , Nagahama Institute of Bio-Science and Technology , Nagahama , Japan.

Bioscience, Biotechnology, and Biochemistry
|July 19, 2014
PubMed

Insights

Tissue factor pathway inhibitor-2 (TFPI-2) suppresses tumors by inhibiting matrix degradation. New research shows Lysine-specific demethylase 2 (LSD2) also regulates TFPI-2, suggesting a role in cancer.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cancer Research

Background:

  • Tissue factor pathway inhibitor-2 (TFPI-2) is a key inhibitor of extracellular matrix degradation and a presumed tumor suppressor.
  • TFPI-2 gene transcription is epigenetically regulated by DNA promoter methylation and histone 3 lysine 4 (H3K4) methylation.
  • Lysine-specific demethylase 1 (LSD1) is known to regulate TFPI-2, but the role of LSD2 is unclear.

Purpose of the Study:

  • To investigate the involvement of LSD2 in the regulation of TFPI-2.
  • To determine if LSD2 affects TFPI-2 expression through epigenetic mechanisms.
  • To compare the roles of LSD1 and LSD2 in TFPI-2 regulation.

Main Methods:

  • Preparation of a monoclonal antibody to specifically detect LSD2.
  • siRNA-mediated knockdown of LSD1 and LSD2 in cells.
  • Measurement of TFPI-2 protein and mRNA levels.
  • Bisulfite sequencing to analyze DNA methylation of the TFPI-2 promoter.

Main Results:

  • siRNA knockdown of either LSD1 or LSD2 individually increased TFPI-2 protein and mRNA levels.
  • Simultaneous knockdown of both LSD1 and LSD2 resulted in additive increases in TFPI-2 expression.
  • TFPI-2 promoter CpG sites were found to be unmethylated, indicating regulation via histone modification rather than DNA methylation.
  • The anti-LSD2 antibody successfully distinguished LSD2 from LSD1.

Conclusions:

  • LSD2, similar to LSD1, contributes to the regulation of TFPI-2 through histone modification.
  • These findings highlight a novel epigenetic regulatory pathway for TFPI-2.
  • Further research into LSD2's role in tumor malignancy is warranted.
Keywords:
histone H3K4 methylationlysine-specific demethylases (LSD1 and LSD2)monoclonal anti-LSD2 antibodytissue factor pathway inhibitor-2 (TFPI-2)

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