miR-655 Is an EMT-suppressive microRNA targeting ZEB1 and TGFBR2.
miR-655 Is an EMT-suppressive microRNA targeting ZEB1 and TGFBR2.
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miR-655是靶向ZEB1和TGFBR2的EMT抑制microRNA。
DOI：
10.1371/journal.pone.0062757
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kozaki K
中科院分区：
文献类型：
--
作者：
Harazono Y;Muramatsu T;Endo H;Uzawa N;Kawano T;Harada K;Inazawa J;Kozaki K
最近，上皮-间充质转化（EMT）已被证明有助于正常和疾病过程，包括癌症的进展。为了探索EMT抑制性microRNAs（miRNAs），我们建立了一个基于细胞的报告系统，该系统使用来自胰腺癌细胞系Panc 1的稳定克隆，该细胞系转染了在ZsGreen 1报告基因5′上游区含有CDH 1/E-cadherin启动子序列的报告构建体。然后，我们使用该系统对470个模拟人类成熟miRNA的合成双链RNA（dsRNA）进行了基于功能的筛选，并将miR-655鉴定为新的EMT抑制性miRNA。miR-655的过表达不仅诱导了E-cadherin的上调和典型EMT诱导物的下调，而且还抑制了间充质样癌细胞的迁移和侵袭，伴随着向上皮表型的形态转变。此外，我们发现miR-655表达与食管鳞状细胞癌（ESCC）的预后良好之间存在显著相关性。此外，ZEB 1和TGFBR 2是TGF-β信号通路的重要组成部分，被鉴定为miR-655的直接靶点，这表明通过miR-655的异常下调激活TGF-β-ZEB 1-E-钙粘蛋白轴可能加速癌症进展。
Recently, the epithelial-to-mesenchymal transition (EMT) has been demonstrated to contribute to normal and disease processes including cancer progression. To explore EMT-suppressive microRNAs (miRNAs), we established a cell-based reporter system using a stable clone derived from a pancreatic cancer cell line, Panc1, transfected with a reporter construct containing a promoter sequence of CDH1/E-cadherin in the 5′ upstream region of the ZsGreen1 reporter gene. Then, we performed function-based screening with 470 synthetic double-stranded RNAs (dsRNAs) mimicking human mature miRNAs using the system and identified miR-655 as a novel EMT-suppressive miRNA. Overexpression of miR-655 not only induced the upregulation of E-cadherin and downregulation of typical EMT-inducers but also suppressed migration and invasion of mesenchymal-like cancer cells accompanied by a morphological shift toward the epithelial phenotype. In addition, we found a significant correlation between miR-655 expression and a better prognosis in esophageal squamous cell carcinoma (ESCC). Moreover, ZEB1 and TGFBR2, which are essential components of the TGF-b signaling pathway, were identified as direct targets of miR-655, suggesting that the activation of the TGF-b-ZEB1-E-cadherin axis by aberrant downregulation of miR-655 may accelerate cancer progression.
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影响因子：
7.8
作者：
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影响因子：
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通讯作者：
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影响因子：
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作者：
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