miR-301a is a candidate oncogene that targets the homeobox gene Gax in human hepatocellular carcinoma

Dig Dis Sci. 2012 May;57(5):1171-80. doi: 10.1007/s10620-012-2099-2. Epub 2012 Feb 29.

Abstract

Background: MicroRNAs (miRNA) are a group of noncoding small RNAs that repress mRNA expression or induce mRNA degradation by binding to the 3'-untranslated regions of mRNAs. MiRNAs have been connected closely with the development of cancers such as hepatocellular carcinoma (HCC). However, the overexpression of microRNA-301a (miR-301a) has seldom been connected with tumorigenesis in HCC.

Aims: This study aims to characterize the function of upregulated miR-301a in HCC and show how the downstream growth arrest-specific homeobox (Gax) is negatively regulated by miR-301a.

Methods: The expression of miR-301a and Gax was detected using real-time PCR on HCC tissues and adjacent non-tumorous tissues. The luciferase reporter assay was used to assess Gax as a target of miR-301a. The nuclear factor κB (NF-κB) was measured by western blot after inhibiting miR-301a and enhancing Gax. The functions of miR-301a in vivo in HCC cells were measured by migration and invasion assays and flow cytometry.

Results: MiR-301a was significantly upregulated and Gax was downregulated in HCC samples compared with in the matching nontumoral tissues. Inhibiting miR-301a expression caused the upregulation of Gax and repressed NF-κB expression. We have shown that miR-301a plays an important role in increasing proliferation, migration and invasion and in inhibiting apoptosis of HCC cells.

Conclusions: miR-301a is frequently upregulated in HCC and modulates NF-κB expression by negatively regulating Gax.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adult
  • Aged
  • Apoptosis / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Homeobox
  • Homeodomain Proteins / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • NF-kappa B / genetics
  • Oncogenes*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation / genetics

Substances

  • 3' Untranslated Regions
  • Homeodomain Proteins
  • MEOX2 protein, human
  • MIRN301A microRNA, human
  • MicroRNAs
  • NF-kappa B
  • RNA, Messenger