MiR-132 suppresses the migration and invasion of lung cancer cells via targeting the EMT regulator ZEB2.
MiR-132 suppresses the migration and invasion of lung cancer cells via targeting the EMT regulator ZEB2.
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MiR-132 通过靶向 EMT 调节因子 ZEB2 抑制肺癌细胞的迁移和侵袭
DOI：
10.1371/journal.pone.0091827
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
You J;Li Y;Fang N;Liu B;Zu L;Chang R;Li X;Zhou Q
微小RNA（microRNAs，miRNAs）是一类小的非编码RNA，在人类肿瘤中可作为癌基因或抑癌基因发挥作用。新的证据表明，miRNAs的失调有助于人类非小细胞肺癌（NSCLC）。在本研究中，我们证明了miR-132的表达水平在检测的NSCLC细胞系和临床NSCLC组织样本中显著降低。随后，我们发现miR-132的导入显著抑制了肺癌细胞的体外迁移和侵袭，提示miR-132可能是一种新的肿瘤抑制因子。进一步的研究表明，EMT相关转录因子ZEB 2是miR-132的直接靶基因之一，其3′非翻译区（3′ UTR）与miR-132直接结合。miR-132可在mRNA和蛋白水平降低ZEB 2的表达。值得注意的是，EMT标志物E-钙粘蛋白或波形蛋白（ZEB 2的下游）也在miR-132处理后下调或上调。此外，过表达或沉默ZEB 2能够提高或抑制肺癌细胞的迁移和侵袭，与miR-132对肺癌细胞的作用平行。同时，ZEB 2的敲低逆转了由anti-miR-132介导的增强的迁移和侵袭。这些结果表明，miR-132通过靶向涉及EMT过程的ZEB 2抑制NSCLC细胞的迁移和侵袭。因此，我们的发现为NSCLC进展的机制提供了新的见解。在治疗上，miR-132可能作为治疗人肺癌的潜在靶点。
MicroRNAs (miRNAs) are small, non-coding RNAs which can function as oncogenes or tumor suppressor genes in human cancers. Emerging evidence reveals that deregulation of miRNAs contributes to the human non-small cell lung cancer (NSCLC). In the present study, we demonstrated that the expression levels of miR-132 were dramatically decreased in examined NSCLC cell lines and clinical NSCLC tissue samples. Then, we found that introduction of miR-132 significantly suppressed the migration and invasion of lung cancer cells in vitro, suggesting that miR-132 may be a novel tumor suppressor. Further studies indicated that the EMT-related transcription factor ZEB2 was one direct target genes of miR-132, evidenced by the direct binding of miR-132 with the 3′ untranslated region (3′ UTR) of ZEB2. Further, miR-132 could decrease the expression of ZEB2 at the levels of mRNA and protein. Notably, the EMT marker E-cadherin or vimentin, a downstream of ZEB2, was also down-regulated or up-regulated upon miR-132 treatment. Additionally, over-expressing or silencing ZEB2 was able to elevate or inhibit the migration and invasion of lung cancer cells, parallel to the effect of miR-132 on the lung cancer cells. Meanwhile, knockdown of ZEB2 reversed the enhanced migration and invasion mediated by anti-miR-132. These results indicate that miR-132 suppresses the migration and invasion of NSCLC cells through targeting ZEB2 involving the EMT process. Thus, our finding provides new insight into the mechanism of NSCLC progression. Therapeutically, miR-132 may serve as a potential target in the treatment of human lung cancer.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
细胞周期蛋白依赖性激酶 4 是 micoRNA-195 介导的膀胱癌细胞细胞周期停滞的新靶点
影响因子：
3.5
作者：
Lin, Yiwei;Wu, Jian;Xie, Liping
通讯作者：
Xie, Liping
影响因子：
8
作者：
Bindels, S.;Mestdagt, M.;Gilles, C.
通讯作者：
Gilles, C.
影响因子：
3.5
作者：
Henrion, Marc;Frampton, Matthew;Houlston, Richard S.
通讯作者：
Houlston, Richard S.
DOI：
10.1016/j.bbrc.2013.01.070
发表时间：
2013-02-22
影响因子：
3.1
作者：
Koopmansch, Benjamin;Berx, Geert;Winkler, Rosita
通讯作者：
Winkler, Rosita