Upregulated microRNA-429 inhibits the migration of HCC cells by targeting TRAF6 through the NF-κB pathway

Oncol Rep. 2017 May;37(5):2883-2890. doi: 10.3892/or.2017.5507. Epub 2017 Mar 15.

Abstract

Increasing evidence indicates that miR-429 is involved in tumor suppression in various human cancers. however, its role in hepatocellular carcinoma (HCC) remains unclear. In the present study, we found that miR-429 was significantly downregulated in HCC tissue samples and cell lines. Upregulation of miR-429 markedly suppressed proliferation and migration of HCC cells. Moreover, we identified TRAF6 as a direct target of miR-429. Downregulation of TRAF6 partially attenuated the oncogenic effect of anti‑miR-429 on HCC cells. Ectopic expression of miR-429 in HCC cells inhibited TCF-4 activity as well as nuclear accumulation of P65 and expression of the NF-κB targets c-Myc and phosphorylation of TAK1. In a nude xenograft model, miR-429 upregulation significantly decreased HCC growth. In conclusion, by targeting TRAF6, miR-429 is downregulated in HCC and inhibits HCC cell proliferation and motility. Our data suggest that miR-429 may serve as a potential anticancer target for the treatment of HCC.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Mice
  • MicroRNAs / genetics*
  • NF-kappa B / genetics
  • Neoplasm Transplantation
  • Signal Transduction
  • TNF Receptor-Associated Factor 6 / genetics*
  • Up-Regulation*

Substances

  • 3' Untranslated Regions
  • Intracellular Signaling Peptides and Proteins
  • MIRN429 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • TNF Receptor-Associated Factor 6
  • Tifab protein, human