MicroRNA-31 inhibits cisplatin-induced apoptosis in non-small cell lung cancer cells by regulating the drug transporter ABCB9

Cancer Lett. 2014 Feb 28;343(2):249-57. doi: 10.1016/j.canlet.2013.09.034. Epub 2013 Oct 4.

Abstract

Alterations in microRNA (miRNA) expression have been found to be involved in tumor growth and response to chemotherapy. However, the possible role of miR-31 in cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC) remains unclear. In this study, we identified a DDP-sensitive and a DDP-resistant cell line from four candidate human NSCLC cell lines. Notably, we found that miR-31 was significantly upregulated in the DDP-resistant cell line compared with its level in the DDP-sensitive cell line. As a result, miR-31 overexpression induced DDP resistance in the DDP-sensitive cell line, and miR-31 knockdown rescued DDP sensitivity in the DDP-resistant cell line. Interestingly, miR-31 was inversely correlated with the expression of the drug resistance gene ABCB9. The luciferase activity assay showed that miR-31 directly targets the 3'UTR of ABCB9, which is known to play a crucial role in drug resistance. Mechanistically, we showed that miR-31 confers DDP-induced apoptosis and that inhibition of ABCB9 is required for DDP resistance. The data demonstrate that miR-31 exerts an anti-apoptotic effect most likely through the inhibition of ABCB9 and thus provide a novel strategy involving the use of miR-31 as a potential target in NSCLC chemotherapy.

Keywords: ABCB9; Apoptosis; Cisplatin resistance; Non-small cell lung cancer; miR-31.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Cell Survival / drug effects
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • MicroRNAs / pharmacology*
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation / drug effects

Substances

  • ABCB9 protein, human
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • MIRN31 microRNA, human
  • MicroRNAs
  • Cisplatin