| 张 勇,叶明翔,张信信,常 宁,韩志萍,熊 洁,张 艰.FBW7泛素化修饰Snail促进上皮间质转化的实验研究[J].,2017,17(30):5844-5848 |
| FBW7泛素化修饰Snail促进上皮间质转化的实验研究 |
| The Ubiquitination of Snail by FBW7 leads to Epithelial-to-Mesenchymal Transition |
| 投稿时间：2017-05-19 修订日期：2017-06-10 |
| DOI：10.13241/j.cnki.pmb.2017.30.010 |
| 中文关键词: FBW7 上皮间质转化 Snail 侵袭转移 |
| 英文关键词: FBW7 EMT Snail Invasion and metastasis |
| 基金项目:国家自然科学基金项目（81272518） |
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| 中文摘要: |
| 摘要 目的：探讨FBW7(F-box/WD repeat-containing protein 7)是否参与转录抑制因子Snail的泛素化修饰，通过调节上皮间质转化(EMT)进而导致非小细胞肺癌的侵袭和转移，为治疗非小细胞肺癌(NSCLC)患者晚期转移提供新的思路。方法：首先，通过Western Blot方法检测多种人肺细胞系中Snail的表达水平。上调(药物处理)及下调(设计并合成特异性shRNA转染)H460细胞中FBW7的表达后，检测Snail的表达水平。采用平板克隆及Transwell方法检测下调FBW7的H460细胞形态改变和侵袭转移能力变化。结果：人非小细胞肺癌H460细胞中Snail表达水平较高。上调FBW7表达可使Snail表达下降，经蛋白酶抑制剂MG132处理后Snail表达升高；而下调FBW7表达后Snail表达增加。下调FBW7表达细胞后，细胞形态改变，侵袭转移能力增强。结论：FBW7参与了Snail泛素化修饰，进而经蛋白酶体途径将其降解引起EMT，导致肿瘤转移和进展的发生。 |
| 英文摘要: |
| ABSTRACT Objective: To explore whether F-box/WD repeat-containing protein 7(FBW7) participates in the ubiquitination of transcription factor, Snail, which leads to epithelial to mesenchymal transition and then induces tumor invasion and metastasis in non small cell lung cancer (NSCLC), and provides new insights for the treatment of advanced NSCLC. Methods: The expression levels of Snail in different lung cancer cell lines are detected by western blot. Up-regulation (drug treatment) and down-regulation (specific siRNAs are designed and synthesized) of FBW7 in H460 lung cancer cell line are applied to detect the variation of Snail expression. Utilization of plate clone formation assay and transwell assay are to confirm morphological changes and the capacity of metastasis and invasion in FBW7-down-regulated H460. Results: Compared with other cell lines, Snail expresses in higher grade. The down-regulation of Snail after enhancement of FBW7 can be blocked by treatment of proteasome inhibitor, MG132, while up-regulation of FBW7 may lead to opposite results. Morphological varieties and enhancement of the ability of metastasis and invasion are proved by down-regulation of FBW7 in H460. Conclusion: FBW7 participates in the ubiquitination of Snail, which in turn is degraded by ubiquitin-proteasome pathway, and then triggers EMT, leading to tumor metastasis and progression. |
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