Roles of lysine-specific demethylase 1 (LSD1) in homeostasis and diseases

J Biomed Sci. 2021 Jun 4;28(1):41. doi: 10.1186/s12929-021-00737-3.

Abstract

Lysine-specific demethylase 1 (LSD1) targets mono- or di-methylated histone H3K4 and H3K9 as well as non-histone substrates and functions in the regulation of gene expression as a transcriptional repressor or activator. This enzyme plays a pivotal role in various physiological processes, including development, differentiation, inflammation, thermogenesis, neuronal and cerebral physiology, and the maintenance of stemness in stem cells. LSD1 also participates in pathological processes, including cancer as the most representative disease. It promotes oncogenesis by facilitating the survival of cancer cells and by generating a pro-cancer microenvironment. In this review, we discuss the role of LSD1 in several aspects of cancer, such as hypoxia, epithelial-to-mesenchymal transition, stemness versus differentiation of cancer stem cells, as well as anti-tumor immunity. Additionally, the current understanding of the involvement of LSD1 in various other pathological processes is discussed.

Keywords: Cancer; Hypoxia; Immunity; Inflammation; Neurodegenerative diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Histone Demethylases / genetics*
  • Histone Demethylases / immunology
  • Histone Demethylases / metabolism
  • Homeostasis / genetics*
  • Homeostasis / immunology
  • Humans
  • Hypoxia / enzymology
  • Hypoxia / genetics
  • Hypoxia / immunology
  • Mice
  • Neoplasms / enzymology
  • Neoplasms / genetics*
  • Neoplasms / immunology
  • Neoplastic Stem Cells / physiology
  • Tumor Escape / genetics

Substances

  • Histone Demethylases
  • KDM1a protein, mouse
  • KDM1A protein, human