Role of IL-6-mediated expression of NS5ATP9 in autophagy of liver cancer cells

J Cell Physiol. 2018 Dec;233(12):9312-9319. doi: 10.1002/jcp.26343. Epub 2018 Jun 26.

Abstract

This study aimed to investigate the relationship between interleukin-6 (IL-6) and NS5ATP9 in autophagy of liver cancer cells. Autophagy is one of the important regulators of the replication of hepatitis C virus and the survival of tumors. IL-6 is a multifunctional cytokine that plays an important role in autophagy and development of many kinds of tumors. However, the role of IL-6 in autophagy has not been fully explored. A previous study had shown that a novel gene, NS5ATP9, could modulate autophagy. The present study demonstrated that human IL-6 recombinant protein induced autophagy of HepG2 cells. Conversely, autophagy decreased after IL-6 was silenced or neutralized with monoclonal antibody against human IL-6. In addition, NS5ATP9 was upregulated by IL-6 via nuclear factor-kappaB activation, as detected by Western blot. Further studies indicated that the induction of autophagy by IL-6 could be attenuated by silencing NS5ATP9. Interestingly, the expression of NS5ATP9, in turn, resulted in the upregulation of IL-6. In conclusion, IL-6 could induce autophagy by expressing NS5ATP9, while NS5ATP9 upregulated IL-6 levels in turn, which further induced autophagy.

Keywords: IL-6; NS5ATP9; autophagy; hepatocellular carcinoma; microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy* / drug effects
  • Autophagy* / genetics
  • Beclin-1 / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Gene Silencing / drug effects
  • Hep G2 Cells
  • Humans
  • Interleukin-6 / metabolism*
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Microtubule-Associated Proteins / metabolism
  • NF-kappa B / metabolism
  • Neutralization Tests
  • Recombinant Proteins / pharmacology
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Beclin-1
  • DNA-Binding Proteins
  • Interleukin-6
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • NF-kappa B
  • PCLAF protein, human
  • Recombinant Proteins