miR-302b suppresses cell invasion and metastasis by directly targeting AKT2 in human hepatocellular carcinoma cells

Tumour Biol. 2016 Jan;37(1):847-55. doi: 10.1007/s13277-015-3330-5. Epub 2015 Aug 8.

Abstract

MicroRNAs (miRNAs) have been shown to play essential roles in regulating the activity of human hepatocellular carcinoma (HCC) cells, thereby contributing to the suppression of invasion and metastasis. In this study, using gain and loss of function assays, we demonstrated that miR-302b was frequently down-regulated in clinical HCC specimens, as compared with 15 corresponding adjacent normal tissues. Overexpression of miR-302b suppressed HCC cell invasion and metastasis. Regulation of NF-κB and matrix metalloproteinase (MMP)-2 expression by miR-302b was mediated via AKT2 in SMMC-7721 cells. Silencing AKT2 produced effects similar to those of miR-302b overexpression, which included inhibiting SMMC-7721 cell invasion and metastasis and dereasing NF-κB and MMP-2 expression. Furthermore, overexpression of AKT2 attenuated the effects of miR-302b overexpression. Taken together, our findings indicate that miR-302b inhibits SMMC-7721 cell invasion and metastasis by targeting AKT2, suggesting that miR-302b might represent a potential therapeutic target for HCC intervention.

Keywords: AKT2; Cell invasion; Cell metastasis; Hepatocellular carcinoma; miR-302b.

MeSH terms

  • 3' Untranslated Regions
  • Carcinoma, Hepatocellular / embryology*
  • Cell Line, Tumor
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • HEK293 Cells
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / metabolism*
  • Matrix Metalloproteinase 2 / metabolism
  • MicroRNAs / metabolism*
  • NF-kappa B / metabolism
  • NF-kappa B p50 Subunit / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins c-akt / metabolism*

Substances

  • 3' Untranslated Regions
  • MIRN302A microRNA, human
  • MicroRNAs
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • AKT2 protein, human
  • Proto-Oncogene Proteins c-akt
  • MMP2 protein, human
  • Matrix Metalloproteinase 2