期刊
CANCER LETTERS
卷 343, 期 2, 页码 249-257出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2013.09.034
关键词
miR-31; ABCB9; Cisplatin resistance; Apoptosis; Non-small cell lung cancer
类别
资金
- Key Scientific Research Fund of Zhejiang Provincial Education Department [Z201119414]
- Natural Science Foundation of Zhejiang Province [Y12C060009]
- Public Technology Research Program of Zhejiang Province [2012C37102]
- Scientific Innovation Team Project of Ningbo [2011B82014]
- Natural Science Foundation of Ningbo City [2012A610193]
- Scientific Research Foundation of Graduate School of Ningbo University [G11JA007, G12JA015]
- Excellent Master Dissertation Cultivation Fund of Ningbo University [PY2012010]
- K.C. Wong Magna Fund at Ningbo University
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.
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