miR-709 up-regulated in hepatocellular carcinoma, promotes proliferation and invasion by targeting GPC5

Cell Prolif. 2015 Jun;48(3):330-7. doi: 10.1111/cpr.12181. Epub 2015 Mar 27.

Abstract

Objectives: Hepatocellular carcinoma (HCC) is one of the most common cancers and is a significant leading cause of cancer-related deaths worldwide. Emerging evidence has shown that microRNAs (miRNAs) are associated with cancer development and progression. However, up to now little has been known concerning the role of miR-709 in HCC.

Materials and methods: Real-time RT-PCR was performed to detect expression of miR-709 in HCC cell lines and tissues. To further understand its role in HCC, we restored its expression in HepG2 cell line through transfection with miR-709 mimics or inhibitors. CCK-8 proliferation assay, migration assay and invasion assay were used to detect functional roles of miR-709. Luciferase assay and western blotting were performed to detect the target gene of miR-709.

Results: We found that miR-709 was highly expressed in HCC tissues and in HCC cell lines by qRT-PCR. Re-expression of miR-709 in HCC cells remarkably promoted cell migration and invasiveness in vitro. Subsequent investigation revealed that glypican-5 (GPC5) was a direct and functional target of miR-709 in HCC cells where overexpression of miR-709 impaired GPC5-induced inhibition of proliferation and invasion. Finally, analysis of miR-709 and GPC5 levels in human HCC tissues revealed that miR-709 inversely correlated with GPC5 expression.

Conclusions: These results suggest that miR-709 may positively regulate invasion and metastasis of HCC through targeting GPC5.

MeSH terms

  • Base Sequence
  • Binding Sites
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Genes, Reporter
  • Glypicans / genetics*
  • Glypicans / metabolism
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Luciferases / genetics
  • Luciferases / metabolism
  • Lymphatic Metastasis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Mimicry
  • Molecular Sequence Data
  • Oligonucleotides / genetics*
  • Oligonucleotides / metabolism
  • Real-Time Polymerase Chain Reaction

Substances

  • GPC5 protein, human
  • Glypicans
  • MicroRNAs
  • Oligonucleotides
  • Luciferases