Li Renyuan, Wu Shengjun, Chen Xin, Xu Hongfei, Teng Peng, Li Weidong
Department of Cardiothoracic Surgery, First Affiliated Hospital of Zhejiang University Hangzhou, China.
Am J Transl Res. 2016 Jun 15;8(6):2512-24. eCollection 2016.
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.
非小细胞肺癌（NSCLC）是全球癌症相关死亡的主要原因之一。含F-box/ WD重复序列蛋白7（FBW7）在人类癌症如胃癌、乳腺癌和肝细胞癌中发挥重要作用。在本研究中，我们发现NSCLC细胞中FBW7的高表达与阿霉素敏感性增加相关。FBW7的下调降低了肿瘤细胞的化学敏感性。Twist是上皮-间质转化（EMT）中的关键转录因子，Twist沉默的NSCLC细胞显示出阿霉素敏感性增加。用阿霉素或缺氧处理细胞可引发EMT，表现为E-钙黏蛋白减少和波形蛋白增加。相反，FBW7的异位表达可防止阿霉素或缺氧诱导的EMT。此外，FBW7被鉴定为NSCLC细胞中miR-223的功能靶点。这些发现确定了miR-223/FBW7通路在调节NSCLC细胞EMT和化学敏感性中的关键作用。
