Expression and Critical Role of Interleukin Enhancer Binding Factor 2 in Hepatocellular Carcinoma

Int J Mol Sci. 2016 Aug 22;17(8):1373. doi: 10.3390/ijms17081373.

Abstract

Interleukin enhancer binding factor 2 (ILF2), a transcription factor, regulates cell growth by inhibiting the stabilization of mRNA. Currently, its role has gained recognition as a factor in the tumorigenic process. However, until now, little has been known about the detailed role ILF2 plays in hepatocellular carcinoma (HCC). In this study, we investigated the expression levels of ILF2 in HCC tissue with Western blot and immunohistochemical assays. To examine the effect of ILF2 on liver cancer cell growth and apoptosis, small interfering RNAs (siRNAs) targeting ILF2 were recombined to create lentiviral overexpression vectors. Our results showed higher expression levels of ILF2 mRNA and ILF2 protein in HCC tissue compared with matched peritumoral tissue. Expression of ILF2 may regulate cell growth and apoptosis in liver cancer cells via regulation of B-cell lymphoma 2 (Bcl-2), Bcl-2 related ovarian killer (Bok), Bcl-2-associated X protein (BAX), and cellular inhibitor of apoptosis 1 (cIAP1). Moreover, we inoculated nude mice with liver cancer cells to investigate the effect of ILF2 on tumorigenesis in vivo. As expected, a rapid growth was observed in cancer cells inoculated with a lentiviral vector coding Flag-ILF2 (Lenti-ILF2) compared with the control cells. Hence, these results promote a better understanding of ILF2's potential role as a therapeutic target in HCC.

Keywords: apoptosis; cell growth; hepatocellular carcinoma; interleukin enhancer binding factor 2.

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / physiopathology*
  • Carcinoma, Hepatocellular / therapy
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Mice
  • Mice, Nude
  • Nuclear Factor 45 Protein / genetics*
  • Nuclear Factor 45 Protein / metabolism*
  • RNA, Small Interfering
  • Signal Transduction
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Ilf2 protein, mouse
  • Inhibitor of Apoptosis Proteins
  • Nuclear Factor 45 Protein
  • RNA, Small Interfering
  • bcl-2-Associated X Protein