IFI16 mis-localization can be a contributing factor to hepatocellular carcinoma progression

Med Hypotheses. 2014 Mar;82(3):398-400. doi: 10.1016/j.mehy.2014.01.017. Epub 2014 Jan 27.

Abstract

Hepatocellular carcinoma (HCC) is a highly deadly cancer, with usually drug resistance. However the mechanisms responsible for this phenomenon are poorly understood. Interferon-γ inducible protein 16 (IFI16), a multifunctional protein, has roles in anti-proliferation, autophagy, cell senescence, anti-inflammation, and DNA sensor to trigger innate immunity. IFI16 physiologically absents in adult healthy hepatocyte, but exists in liver cancer cells. Interestingly, increasing evidences suggest that dysregulation or/and loss of IFI16 function have a critical role in drug resistance and tumor progression. Furthermore, interaction with DNA or other protein depends on IFI16 localization. In our study, to our knowledge, we first showed that IFI16 is a chromatin-binding protein in four HCC cell lines with different TP53 genotype, but not in fetal liver cell line, L02 cells. However, the function of IFI16 subcellular localization has not been determined in HCC. Therefore, we present our study and theoretical basis and presume that chromatin-bounding localization of IFI16 is associated with HCC progression. If we are able to acetylate or/and delete NLS of IFI16 with activated-p53 restoration, we may offer an alternative for HCC therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Chromatin / metabolism
  • DNA Primers
  • Disease Progression
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Models, Theoretical
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Subcellular Fractions / metabolism

Substances

  • Chromatin
  • DNA Primers
  • Nuclear Proteins
  • Phosphoproteins
  • IFI16 protein, human