miR-93 promotes TGF-β-induced epithelial-to-mesenchymal transition through downregulation of NEDD4L in lung cancer cells.
miR-93 promotes TGF-β-induced epithelial-to-mesenchymal transition through downregulation of NEDD4L in lung cancer cells.
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DOI：
10.1007/s13277-015-4328-8
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Wang QE
中科院分区：
文献类型：
--
作者：
Qu MH;Han C;Srivastava AK;Cui T;Zou N;Gao ZQ;Wang QE
肿瘤中microRNA-93（miR-93）的水平最近被报道与肺癌患者的生存率呈负相关。考虑到肺癌最具破坏性的方面是转移，其可以通过转化生长因子-β（TGF-β）诱导的上皮向间充质转化（EMT）来促进，我们试图确定miR-93是否参与该过程。在这里，我们报告了一个以前未鉴定的miR-93靶点，神经前体细胞表达发育下调基因4样（NEDD 4L），能够介导肺癌细胞中TGF-β介导的EMT。miR-93直接与NEDD 4L信使RNA（mRNA）的3′-UTR结合，导致NEDD 4L在蛋白水平表达下调。我们接下来证明了NEDD 4L的下调增强，而NEDD 4L的过表达减少TGF-β信号传导，这反映在TGF-β处理后肺癌细胞系中SMAD 2的磷酸化增加。此外，肺癌细胞中miR-93的过表达通过下调NEDD 4L促进TGF-β诱导的EMT。对公开可用的基因表达阵列数据集的分析表明，低NEDD 4L表达与肺癌患者的不良结局相关，进一步支持miR-93在肺肿瘤发生和转移中的致癌作用。
The level of microRNA-93 (miR-93) in tumors has been recently reported to be negatively correlated with survival of lung cancer patients. Considering that the most devastating aspect of lung cancer is metastasis, which can be promoted by transforming growth factor-β (TGF-β)-induced epithelial- to-mesenchymal transition (EMT), we sought to determine whether miR-93 is involved in this process. Here, we report that a previously unidentified target of miR-93, neural precursor cell expressed developmentally downregulated gene 4-like (NEDD4L), is able to mediate TGF-β-mediated EMT in lung cancer cells. miR-93 binds directly to the 3′-UTR of the NEDD4L messenger RNA (mRNA), leading to a downregulation of NEDD4L expression at the protein level. We next demonstrated that the downregulation of NEDD4L enhanced, while overexpression of NEDD4L reduced TGF-β signaling, reflected by increased phosphorylation of SMAD2 in the lung cancer cell line after TGF-β treatment. Furthermore, overexpression of miR-93 in lung cancer cells promoted TGF-β- induced EMT through downregulation of NEDD4L. The analysis of publicly available gene expression array datasets indicates that low NEDD4L expression correlates with poor outcomes among patients with lung cancer, further supporting the oncogenic role of miR-93 in lung tumorigenesis and metastasis.
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影响因子：
3.5
作者：
Goel P;Manning JA;Kumar S
通讯作者：
Kumar S
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影响因子：
3.7
作者：
Dahlberg, Jonas;Nilsson, Lars-Olof;von Wowern, Fredrik;Melander, Olle
通讯作者：
Melander, Olle
影响因子：
5.8
作者：
Robinson, Kyle W.;Sandler, Alan B.
通讯作者：
Sandler, Alan B.
影响因子：
--
作者：
Tang, Qingchao;Zou, Zhaoxia;Wang, Xishan
通讯作者：
Wang, Xishan
影响因子：
37.3
作者：
Lyu X;Fang W;Cai L;Zheng H;Ye Y;Zhang L;Li J;Peng H;Cho WC;Wang E;Marincola FM;Yao K;Cai H;Li J;Li X
通讯作者：
Li X