miR-639 regulates transforming growth factor beta-induced epithelial-mesenchymal transition in human tongue cancer cells by targeting FOXC1.
miR-639 regulates transforming growth factor beta-induced epithelial-mesenchymal transition in human tongue cancer cells by targeting FOXC1.
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miR-639 通过靶向 FOXC1 来调节人舌癌细胞中转化生长因子 β 诱导的上皮间质转化。
DOI：
10.1111/cas.12499
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发表时间：
2014-10
期刊：
影响因子：
5.7
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Lin Z;Sun L;Chen W;Liu B;Wang Y;Fan S;Li Y;Li J
上皮-间充质转化（EMT）与胚胎发育和各种病理事件有关。据报道，转化生长因子β (TGFβ)在肿瘤细胞中诱导EMT，这是导致肿瘤扩散和治疗失败的转移过程中的关键步骤。然而，microRNA在舌鳞状细胞癌（TSCC）的EMT过程中的参与仍有待确定。为了解决这个问题，我们用人重组TGFβ1处理TSCC细胞系SCC9和CAL27 48小时。miRNA芯片显示，tgf β处理的SCC9细胞中miR-639显著下调。miR-639与miRNA模拟物异位表达可有效阻断tgf β诱导的SCC9和CAL27细胞中的EMT，但使用反义寡核苷酸抑制SCC9和CAL27细胞中的miR-639可诱导EMT。计算microRNA靶标预测检测到FOXC1 mRNA 3 ' -UTR中与miR-639种子区匹配的保守序列。荧光素酶报告基因检测显示miR-639靶向FOXC1。FOXC1异位表达诱导TSCC细胞EMT。沉默FOXC1表达可阻断tgf β诱导的SCC9细胞EMT。在临床上，miR-639表达降低与TSCC的转移和较差的患者生存有关。本研究的数据表明，miR-639的表达降低强调了tgf β通过靶向FOXC1在TSCC中诱导EMT的机制，并可能在转移过程中作为治疗靶点。
Epithelial-to-mesenchymal transition (EMT) is implicated in embryonic development and various pathological events. Transforming growth factor beta (TGFβ) has been reported to induce EMT in tumor cells, which is a critical step in the process of metastasis leading to cancer spreading and treatment failure. However, the involvement of microRNA during the EMT process in tongue squamous cell carcinoma (TSCC) remains to be determined. To address this question, TSCC cell lines SCC9 and CAL27 were treated with human recombinant TGFβ1 for 48 h. miRNA microarray illustrated that miR-639 was significantly downregulated in TGFβ-treated SCC9 cells. Ectopic expression of miR-639 with miRNA mimics effectively blocked TGFβ-induced EMT in SCC9 and CAL27 cells, but inhibition of miR-639 in SCC9 and CAL27 cells with antisense oligonucleotides induced EMT. Computational microRNA target predictions detected a conserved sequence matching to the seed region of miR-639 in the 3′-UTR of FOXC1 mRNA. Luciferase reporter assays revealed that miR-639 targets FOXC1. Ectopic expression of FOXC1 induces EMT in TSCC cells. Silencing FOXC1 expression blocked TGFβ-induced EMT in SCC9 cells. Clinically, reduced miR-639 expression was associated with metastasis in TSCC and poor patient survival. The data from the present study suggest that reduced expression of miR-639 underscores the mechanism of TGFβ-induced EMT in TSCC by targeting FOXC1 and may serve as therapeutic targets in the process of metastasis.
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影响因子：
21.3
作者：
Wellner, Ulrich;Schubert, Joerg;Brabletz, Thomas
通讯作者：
Brabletz, Thomas
影响因子：
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作者：
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Inman, Gareth J.
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影响因子：
8
作者：
Sun, L.;Yao, Y.;Li, J.
通讯作者：
Li, J.
影响因子：
3.8
作者：
Du, Juan;Li, Lin;Lu, Jun
通讯作者：
Lu, Jun