Fusaric acid-induced epigenetic modulation of hepatic H3K9me3 triggers apoptosis in vitro and in vivo

Epigenomics. 2020 Jun;12(11):955-972. doi: 10.2217/epi-2019-0284. Epub 2020 Aug 7.

Abstract

Aim: To determine the effect of the food-borne mycotoxin, fusaric acid (FA) on miR-200a, SUV39H1-mediated H3K9me3, genome integrity and apoptosis in human liver (HepG2) cells and C57BL/6 mice livers. Materials & methods: MiR-200a, Sirt1, SUV39H1-mediated H3K9me3, genome integrity and apoptosis was measured in HepG2 cells and C57BL/6 mice livers using qPCR, western blot, DNA electrophoresis and luminometry. Results: FA: upregulated miR-200a and decreased Sirt1 expression in HepG2 cells and mice livers; decreased expression of SUV39H1 and KDM4B, thus decreasing H3K9me3 and increasing H3K9me1; increased cell mortality via apoptosis. Conclusion: FA induced apoptosis by upregulating miR-200a and decreasing SUV39H1-mediated H3K9me3 in HepG2 cells and mice livers.

Keywords: H3K9me1; H3K9me3; KDM4B; MiR-200a; SUV39H1; Sirt1; apoptosis; fusaric acid; genome instability; p-S139-H2Ax.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Down-Regulation
  • Epigenesis, Genetic*
  • Fusaric Acid / pharmacology*
  • Hep G2 Cells
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Liver / drug effects*
  • Male
  • Methyltransferases / genetics
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • Repressor Proteins / genetics
  • Sirtuin 1 / genetics
  • Up-Regulation

Substances

  • MIRN200 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • Jumonji Domain-Containing Histone Demethylases
  • KDM4B protein, human
  • SUV39H1 protein, human
  • Methyltransferases
  • SIRT1 protein, human
  • Sirtuin 1
  • Fusaric Acid