title: miR-223/FBW7 axis regulates doxorubicin sensitivity through epithelial mesenchymal transition in non-small cell lung cancer.
abstract: 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.
authors.affiliation: Department of Cardiothoracic Surgery, First Affiliated Hospital of Zhejiang University Hangzhou, China.
authors.forename: Renyuan
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Cardiothoracic Surgery, First Affiliated Hospital of Zhejiang University Hangzhou, China.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Cardiothoracic Surgery, First Affiliated Hospital of Zhejiang University Hangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Cardiothoracic Surgery, First Affiliated Hospital of Zhejiang University Hangzhou, China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Cardiothoracic Surgery, First Affiliated Hospital of Zhejiang University Hangzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Teng
authors.affiliation: Department of Cardiothoracic Surgery, First Affiliated Hospital of Zhejiang University Hangzhou, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
keywords: FBW7; Non-small cell lung cancer; drug resistance; epithelial-mesenchymal transition; miR-223