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- Zhuo Dong, Zhiwei Zhong, Lihua Yang, Shaomin Wang, and Zhaohui Gong.
- Institute of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China.
- Cancer Lett. 2014 Feb 28; 343 (2): 249-57.
AbstractAlterations 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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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