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miR‐495 Enhances the Sensitivity of Non‐Small Cell Lung Cancer Cells to Platinum by Modulation of Copper‐Transporting P‐type Adenosine Triphosphatase A (ATP7A)
Author(s) -
Song Liqiang,
Li Yan,
Li Weina,
Wu Shouzhen,
Li Zhikui
Publication year - 2014
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24665
Subject(s) - atp7a , gene knockdown , cancer research , microrna , cisplatin , chemistry , cell , western blot , microbiology and biotechnology , lung cancer , biology , gene , atpase , biochemistry , medicine , enzyme , genetics , chemotherapy
Copper‐transporting P‐type adenosine triphosphatase A (ATP7A) is associated with platinum drug resistance in non‐small cell lung cancer (NSCLC). microRNAs (miRNAs) are a class of small non‐coding RNA molecules that regulate gene expression at post‐transcriptional level. In this study, the aim is to explore which miRNAs might participate in the platinum resistance by targeting ATP7A in NSCLC. Using real‐time PCR‐based miRNA expression profiling and bioinformatics, we selected miR‐495 as a candidate miRNA. EGFP reporter assay, real‐time PCR, and Western blot validated that ATP7A was a direct target for miR‐495. The drug sensitivity assay indicated that miR‐495 enhanced the cell response to cisplatin (CDDP) in NSCLC cells, while inhibition of miR‐495 led to the opposite effects. Importantly, either overexpression or knockdown of ATP7A could override the effect of miR‐495 on chemosensitivity. We also demonstrated that miR‐495 increased the intracellular CDDP accumulation and overexpression of ATP7A can reduce the increased drug concentration induced by miR‐495. Finally, we discovered that there was a converse relationship between miR‐495 and ATP7A levels in NSCLC tissues sensitive or resistant to CDDP. In conclusion, our data demonstrate that miR‐495 regulates the multi‐drug resistance by modulation of ATP7A expression in NSCLC and suggest that miR‐495 may serve as a potential biomarker for the treatment of multi‐drug resistant NSCLC patients with high ATP7A levels. J. Cell. Biochem. 115: 1234–1242, 2014. © 2013 Wiley Periodicals, Inc.