LncRNA GAS5 enhanced the killing effect of NK cell on liver cancer through regulating miR-544/RUNX3

Innate Immun. 2019 Feb;25(2):99-109. doi: 10.1177/1753425919827632.

Abstract

This study aimed to explore the role of lncRNA GAS5 in the regulation of the killing effect of NK cells on liver cancer. Compared with a control group, lncRNA GAS5, RUNX3, and NCR1 were down-regulated in NK cells of patients with liver cancer, whereas miR-544 expression was up-regulated in NK cells of patients with liver cancer. Activated NK cells had higher IFN-γ level. Knockdown of GAS5 in activated NK cells decreased IFN-γ secretion, NK cell cytotoxicity, the percentage of CD107a+ NK cells, and the apoptosis rate of HepG2 and Huh7 cells. We also proved the interaction of GAS5 and miR-544, and the negative regulation role of GAS5 on miR-544. GAS5 overexpression in activated NK cells increased RUNX3 expression, IFN-γ secretion, the NK cell cytotoxicity, the percentage of CD107a+ NK cells, and the apoptosis rate of HepG2 cells, while miR-544 mimic abolished the promotion effect of GAS5 overexpression. Finally, in vivo experiments indicated an inhibition effect of GAS5 in tumor growth. LncRNA GAS5 overexpression enhances the killing effect of NK cell on liver cancer through regulating miR-544/RUNX3.

Keywords: RUNX3; liver cancer; lncRNA GAS5; miR-544; natural killer cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Core Binding Factor Alpha 3 Subunit / genetics
  • Core Binding Factor Alpha 3 Subunit / metabolism*
  • Cytotoxicity, Immunologic
  • Gene Expression Regulation
  • Hep G2 Cells
  • Humans
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology*
  • Liver Neoplasms / genetics*
  • Lymphocyte Activation
  • Lysosomal-Associated Membrane Protein 1 / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Natural Cytotoxicity Triggering Receptor 1 / genetics
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism
  • Neoplasms, Experimental
  • RNA, Long Noncoding / genetics*

Substances

  • Core Binding Factor Alpha 3 Subunit
  • Lysosomal-Associated Membrane Protein 1
  • MIRN544 microRNA, human
  • MicroRNAs
  • NCR1 protein, human
  • Natural Cytotoxicity Triggering Receptor 1
  • RNA, Long Noncoding
  • Runx3 protein, human
  • Interferon-gamma