MiR-145 reduces ADAM17 expression and inhibits in vitro migration and invasion of glioma cells.

MiR-145 reduces ADAM17 expression and inhibits in vitro migration and invasion of glioma cells.
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DOI:
10.3892/or.2012.2084
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发表时间:
2013-01
期刊:
影响因子:
4.2
通讯作者:
Jiang F
Jiang F
中科院分区:
医学3区
文献类型:
--
作者:
Lu Y;Chopp M;Zheng X;Katakowski M;Buller B;Jiang F

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microRNA是基因表达的重要调节因子,在肿瘤发生中起着关键作用。在这项研究中,我们发现,与正常脑组织相比,miR-145在胶质瘤细胞系中显著下调,并负调控肿瘤发生。胶质瘤细胞中miR-145的恢复显著降低了体外增殖、迁移和侵袭。此外,miR-145的过表达降低了ADAM 17和EGFR的表达。此外,我们测试了miR-145介导的细胞增殖、迁移和侵袭抑制至少部分是由于ADAM 17和EGFR基因表达沉默的假设。利用携带ADAM 17 3′-非翻译区的荧光素酶报告基因结合蛋白质印迹法,我们鉴定了ADAM 17是miR-145的直接靶点。总的来说,这些结果表明,作为一种肿瘤抑制因子,miR-145不仅抑制肿瘤增殖,而且抑制细胞迁移和侵袭,值得进一步研究。
MicroRNAs are important regulators of gene expression and have been suggested to play a key role in tumorigenesis. In this study, we show that miR-145 is significantly downregulated in glioma cell lines compared to normal brain tissue and negatively regulates tumorigenesis. Restoration of miR-145 in glioma cells significantly reduced in vitro proliferation, migration and invasion. Also, overexpression of miR-145 reduced ADAM17 and EGFR expression. In addition, we tested the hypothesis that the miR-145-mediated suppression of cell proliferation, migration and invasion is, at least in part, due to silencing of ADAM17 and EGFR gene expression. Using luciferase reporters carrying the 3′-untranslated region of ADAM17 combined with western blotting, we identified ADAM17 as a direct target of miR-145. Collectively, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor proliferation, but also cell migration and invasion, and warrants further investigation.
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