MicroRNA-145 inhibits cell proliferation by directly targeting ADAM17 in hepatocellular carcinoma

Oncol Rep. 2014 Nov;32(5):1923-30. doi: 10.3892/or.2014.3424. Epub 2014 Aug 20.

Abstract

MicroRNAs (miRNAs) are key regulators in cell processes. Emerging evidence has suggested that there is a direct association between miRNAs and cancer. However, the exact regulatory mechanisms of miRNAs in tumorigenesis are poorly understood. In the present study, we showed that miR-145 is able to significantly reduce mRNA and protein expression levels of A disintegrin and metalloproteinase 17 (ADAM17) in liver cancer cells (SMMC-7721, BEL-7402 and Huh-7). Dual luciferase reporter assays confirmed that ADAM17 is a direct target of miR-145. Notably, we found that miR-145 inhibits cell proliferation and growth activity in SMMC-7721 cells. These results demonstrated that it may be exert the function of tumor suppression in a particular link of cancer cell growth. Further studies revealed that the silencing of ADAM17 decreased the proliferation and growth activity of SMMC-7721 cells. Moreover, it reduced the expression of MMP-9. In conclusion, miR-145 inhibits liver cancer cell proliferation by directly targeting ADAM17. Thus, it may become a promising biological target in the treatment strategy of hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / antagonists & inhibitors*
  • ADAM Proteins / genetics
  • ADAM17 Protein
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • HEK293 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Matrix Metalloproteinase 9 / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*

Substances

  • MIRN145 microRNA, human
  • MicroRNAs
  • ADAM Proteins
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • ADAM17 Protein
  • ADAM17 protein, human