Knockdown of D-dopachrome Tautomerase Inhibits Cell Proliferation in Human HepG2 Cell Line

Anticancer Res. 2021 Aug;41(8):4077-4082. doi: 10.21873/anticanres.15209.

Abstract

Background/aim: D-dopachrome tautomerase (DDT) is a macrophage migration inhibitory factor (MIF) homolog that promotes cell growth via CD74, a MIF cell surface receptor, in some types of tumors. We previously found that DDT acts as an anti-obesity adipokine independent of MIF. To understand the intrinsic properties of these two cytokines, a comparison of their actions in various tissues is necessary. In this study, we investigated the involvement of DDT in HepG2 cell (a human hepatoma cell line) proliferation, which is known to be promoted by MIF.

Materials and methods: Cell proliferation and gene expression were evaluated in HepG2 cells expressing short hairpin RNA against the DDT gene.

Results: Inhibition of cell proliferation and reduced expression levels of cyclin D1 were observed in DDT-knockdown HepG2 cells. The inhibited proliferation was restored by administration of recombinant DDT.

Conclusion: DDT promotes cell proliferation in HepG2 cells; therefore, its action may be similar to that of MIF.

Keywords: Adipokine; apoptosis; cell proliferation; liver cancer.

MeSH terms

  • Cell Proliferation / genetics*
  • Cell Survival
  • Cyclin D1 / genetics
  • Gene Knockdown Techniques
  • Hep G2 Cells
  • Humans
  • Intramolecular Oxidoreductases / genetics*

Substances

  • CCND1 protein, human
  • Cyclin D1
  • Intramolecular Oxidoreductases
  • dopachrome isomerase