microRNA-1274a, a modulator of sorafenib induced a disintegrin and metalloproteinase 9 (ADAM9) down-regulation in hepatocellular carcinoma

FEBS Lett. 2011 Jun 23;585(12):1828-34. doi: 10.1016/j.febslet.2011.04.040. Epub 2011 Apr 23.

Abstract

Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with poor prognosis. Sorafenib, a multikinase inhibitor, has been widely used to treat patients with advanced HCC in clinic. We postulated that microRNAs (miRNA) might be involved in HCC target-chemotherapy with sorafenib. MiRNA profile of HepG2 was evaluated after cells were treated with vehicle or sorafenib and alterations in miRNA expression occurred with 14 miRNAs. MiR-1274a, which is up-regulated by sorafenib, could significantly repress expression of ADAM9, a protease that is involved in sorafenib target-therapy of HCC, in HCC cells. Taken together, our data emphasizes a new miRNA-based mechanism of sorafenib antitumor therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics*
  • Antineoplastic Agents / pharmacology*
  • Benzenesulfonates / pharmacology*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Down-Regulation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Membrane Proteins / genetics*
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Protein Kinase Inhibitors / pharmacology*
  • Pyridines / pharmacology*
  • Sorafenib

Substances

  • Antineoplastic Agents
  • Benzenesulfonates
  • Membrane Proteins
  • MicroRNAs
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Pyridines
  • Niacinamide
  • Sorafenib
  • ADAM Proteins
  • ADAM9 protein, human