Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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MiR-130a Overcomes Gefitinib Resistance by Targeting Met in Non-Small Cell Lung Cancer Cell Lines

  • Zhou, Yong-Ming (Department of Geriatrics, Wuhan University, Renmin Hospital) ;
  • Liu, Juan (Department of Geriatrics, Wuhan University, Renmin Hospital) ;
  • Sun, Wei (Department of Thoracic Surgery, Tongji Hospital of Huazhong University of Science and Technology)
  • Published : 2014.02.01
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Abstract

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the most common cause of lung cancer death. Currently, the epidermal growth factor receptor inhibitor gefitinib is used for its treatment; however, drug resistance is a major obstacle. Expression of Met has been associated with both primary and acquired resistance to gefitinib, but the mechanisms regulating its expression are not fully understood. Recently, miRNAs such as miR-130a have been shown to play a role in gefitinib resistance, but importance in NSCLC and relationships with Met have not been fully explored. Here we show that miR-130a is over-expressed in gefitinibsensitive NSCLC cell lines, but is low in gefitinib-resistant NSCLC cell lines. Moreover, miR-130a expression was negatively correlated with that of Met. Further analysis revealed that over-expression of miR-130a increased cell apoptosis and inhibited proliferation of NSCLC cells treated with gefitinib, whereas lowering the expression of miR-130a decreased cell apoptosis and promoted cell proliferation after treatment with gefitinib in both gefitinib-sensitive and -resistant NSCLC cell lines, suggesting that miR-130a overcomes gefitinib resistance. We also demonstrated that miR-130a binds to the 3'-UTR of Met and significantly suppresses its expression. Finally, our results showed that over-expressing Met could "rescue" the functions of miR-130a regarding cell apoptosis and proliferation after cells are treated with gefitinib. These findings indicate that the miR-130a/Met axis plays an important role in gefitinib resistance in NSCLC. Thus, the miR-130a/Met axis may be an effective therapeutic target in gefitinib-resistant lung cancer patients.

Keywords

References

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