Human nonsense-mediated RNA decay regulates EMT by targeting the TGF-ss signaling pathway in lung adenocarcinoma
Human nonsense-mediated RNA decay regulates EMT by targeting the TGF-ss signaling pathway in lung adenocarcinoma
复制标题
人类无义介导的 RNA 衰变通过靶向肺腺癌中的 TGF-α 信号通路来调节 EMT
DOI：
10.1016/j.canlet.2017.06.021
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发表时间：
2017-09-10
期刊：
影响因子：
9.7
通讯作者：
Cao, Wenfeng
中科院分区：
文献类型：
--
作者：
Cao, Lu;Qi, Lisha;Cao, Wenfeng
无义介导的mRNA衰变（NMD）是一种高度保守的选择性降解异常RNA转录物的途径。本研究证实NMD对肺腺癌上皮-间质转化（EMT）的调控作用。此外，我们发现NMD核心因子UP-移码1在人ADC组织中的表达水平往往低于正常肺组织，从而提高了NMD下调以允许ADC肿瘤发生的可能性。我们在人ADC细胞系中的实验表明，下调NMD可以促进EMT。此外，EMT可以通过上调NMD来抑制。我们测试了TGF-β信号传导的作用，发现NMD通过靶向TGF-β信号传导途径影响EMT。我们的研究结果表明，NMD是一种潜在的肿瘤调控机制，可能是ADC的一个潜在的治疗靶点。(C)2017爱思唯尔B. V.保留所有权利。
Nonsense-mediated mRNA decay (NMD) is a highly conserved pathway that selectively degrades aberrant RNA transcripts. In this study, we proved that NMD regulates the epithelial-mesenchymal transition (EMT) of lung adenocarcinoma (ADC). Moreover, we found that NMD core factor UP-frameshift 1 tends to be expressed at lower levels in human ADC tissues than in normal lung tissues, thereby raising the possibility that NMD may be downregulated to permit ADC oncogenesis. Our experiments in human ADC cell lines showed that downregulating NMD can promote EMT. Moreover, EMT can be inhibited by upregulating NMD. We tested the role of TGF-ss signaling and found that NMD influences EMT by targeting the TGF-ss signaling pathway. Our findings reveal that NMD is a potential tumor regulatory mechanism and may be a potential therapeutic target for ADC. (C) 2017 Elsevier B.V. All rights reserved.