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  • 标题:Lysyl oxidase expression is regulated by the H3K27 demethylase Jmjd3 in tumor-associated M2-like macrophages
  • 本地全文:下载
  • 作者:Ryuhei Takemoto ; Tetsuro Kamiya ; Hirokazu Hara
  • 期刊名称:Journal of Clinical Biochemistry and Nutrition
  • 印刷版ISSN:0912-0009
  • 电子版ISSN:1880-5086
  • 出版年度:2020
  • 卷号:66
  • 期号:2
  • 页码:110-115
  • DOI:10.3164/jcbn.19-67
  • 出版社:The Society for Free Radical Research Japan
  • 摘要:Copper is one of the essential micronutrients, and copper-containing enzymes contribute to crucial functions in the body. Lysyl oxidase is a copper-containing enzyme that remodels the extracellular matrix by cross-linking collagen and elastin. The overexpression of lysyl oxidase was recently shown to promote tumor metastasis. M2-like macrophages were also found to significantly accumulate in the tumor microenvironment, and correlated with a poor patient’s outcome. We speculate that M2-like macrophages promote tumor progression via lysyl oxidase expression. Epigenetics, a mitotically heritable change in gene expression without any change in DNA sequencing, is also associated with tumor progression. However, the relationship between lysyl oxidase expression in M2-like macrophages and epigenetics remains unclear. Lysyl oxidase expression was significantly induced in human leukemic THP-1 cell-derived M2-like macrophages. Furthermore, the level of histone H3 tri-methylation at lysine 27 was decreased, and a pre-treatment with a H3K27 demethylase inhibitor notably suppressed lysyl oxidase expression in M2-like macrophages. Lysyl oxidase derived from M2-like macrophages also enhanced breast cancer cell migration, and this was suppressed by a H3K27 demethylase inhibitor. The present results suggest the mechanism of lysyl oxidase expression in M2-like macrophages as an aspect of epigenetics, particularly histone methylation..
  • 关键词:lysyl oxidase;M2;like macrophages;epigenetics
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