miR-223/FBW7 axis regulates doxorubicin sensitivity through epithelial mesenchymal transition in non-small cell lung cancer
Non-small cell lung cancer(NSCLC)is one of the leading causes of cancer-related deaths in the world.F-box/WD repeat-containing protein 7(FBW7)plays important roles in human cancers,such as gastric cancer,breast cancer,and hepatocellular carcinoma.In this study,we found that high levels of FBW7 expression were associated with increased doxorubicin sensitivity in NSCLC cells.Down-regulation of FBW7 reduced the chemosensitivity in tumor cells.Twist is a critical transcription factor in epithelial-mesenchymal transition(EMT),and NSCLC cells with silenced Twist showed increased doxorubicin sensitivity.Treatment of cells with doxorubicin or hypoxia was shown to trigger EMT as evidenced by decreased E-cadherin and increased Vimentin.In contrast,ectopic expression of FBW7 prevented doxorubicin-or hypoxia-induced EMT.In addition,FBW7 was identified as a functional target of miR-223 in NSCLC cells.These findings define a critical role of miR-223/FBW7 pathway in regulating EMT and chemosensitivity in NSCLC cells.
non-small cell lung cancer drug resistance miR-223 FBW7 epithelial-mesenchymal transition
Renyuan Li Shengjun Wu Xin Chen Hongfei Xu Peng Teng Weidong Li
Department of Cardiothoracic Surgery,First Affiliated Hospital of Zhejiang University,Hangzhou,China
国内会议
浙江湖州
英文
1-29
2016-08-05（万方平台首次上网日期，不代表论文的发表时间）