MiR-30a-5p suppresses cell growth and enhances apoptosis of hepatocellular carcinoma cells via targeting AEG-1

Int J Clin Exp Pathol. 2015 Dec 1;8(12):15632-41. eCollection 2015.

Abstract

Background: MiR-30a-5p has been reported to play vital roles in the carcinogenesis and progression of various malignancies via different molecular mechanisms. However, the role and target genes of miR-30a-5p in hepatocellular carcinoma (HCC) remain still unclear. In silico analysis finds that there are complementary sequences between the 3'-untrasnlated region of astrocyte elevated gene 1 (AEG-1) and miR-30a-5p. Herein, we investigated the biological function of miR-30a-5p, as well as the potential molecular mechanism via targeting AEG-1 in HCC cells.

Materials and methods: MiR-30a-5p inhibitor, miR-30a-5p mimic, AEG-1 siRNAs, as well as their negative controls were transfected into HCC cell lines HepG2, SMMC-7221, HepB3 and SNU449. Then, the in vitro influence and mechanism of miR-30a-5p on cell viability, proliferation, caspase-3/7 activity and apoptosis were studied, as assessed by different methods, including spectrophotometry, fluorimetry, fluorescence microscopy of Hoechst 33342/propidium iodide double chromatin staining, western blot and dual luciferase reporter assay, respectively.

Results: MiR-30a-5p mimic markedly inhibited cell growth, also induced caspase-3/7 activity and apoptosis in all four HCC cell lines tested. The strongest effect was observed in HepG2 and SMMC-7721 cells. However, this effect was slightly weaker than that of AEG-1 siRNAs. Transfection of miR-30a-5p mimic led to a markedly reduced AEG-1 protein level and further dual luciferase reporter assay confirmed that AEG-1 was one of the target genes of miR-30a-5p in HCC cells.

Conclusions: MiR-30a-5p may play an essential role in the cell growth and apoptosis of HCC cells, partially via targeting AEG-1.

Keywords: AEG-1; apoptosis; caspase; cell growth; hepatocellular carcinoma; miR-30a-5p.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis*
  • Binding Sites
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Proliferation*
  • Cell Survival
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Membrane Proteins
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA Interference
  • RNA-Binding Proteins
  • Signal Transduction
  • Time Factors
  • Transfection

Substances

  • 3' Untranslated Regions
  • Cell Adhesion Molecules
  • MIRN30b microRNA, human
  • MTDH protein, human
  • Membrane Proteins
  • MicroRNAs
  • RNA-Binding Proteins
  • CASP3 protein, human
  • CASP7 protein, human
  • Caspase 3
  • Caspase 7