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

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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.