Upregulated miR-130a increases drug resistance by regulating RUNX3 and Wnt signaling in cisplatin-treated HCC cell

Biochem Biophys Res Commun. 2012 Aug 24;425(2):468-72. doi: 10.1016/j.bbrc.2012.07.127. Epub 2012 Jul 27.

Abstract

Cisplatin is one of the commonly used chemotherapeutic drugs for the treatment of patients with advanced liver cancer. However, acquisition of cisplatin resistance is common in patients with hepatocellular carcinoma (HCC), and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-130a levels were significantly increased in HCC patients treated with cisplatin-based chemotherapy. miR-130a levels were also higher in cisplatin-resistant Huh7 cells than in Huh7 cells. Overexpression of miR-130a contributed to cisplatin resistance in Huh7 cell, whereas knockdown of miR-130a overcame cisplatin resistance in cisplatin-resistant Huh7 cell. We further demonstrated that upregulated miR-130a directly inhibited expression of tumor suppressor gene RUNX3, which resulted in activation of Wnt/β-catenin signaling and increased drug resistance. These data suggest that miR-130a/RUNX3/Wnt signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.

MeSH terms

  • Aged
  • Antineoplastic Agents / pharmacology
  • Carcinoma, Hepatocellular / metabolism*
  • Cisplatin / pharmacology
  • Core Binding Factor Alpha 3 Subunit / biosynthesis*
  • Drug Resistance, Neoplasm*
  • Female
  • HEK293 Cells
  • Humans
  • Liver Neoplasms / metabolism*
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Wnt Signaling Pathway*

Substances

  • Antineoplastic Agents
  • Core Binding Factor Alpha 3 Subunit
  • MIRN130 microRNA, human
  • MicroRNAs
  • Runx3 protein, human
  • Cisplatin