miR-5100 promotes tumor growth in lung cancer by targeting Rab6
miR-5100 promotes tumor growth in lung cancer by targeting Rab6
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DOI：
10.1016/j.canlet.2015.03.004
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发表时间：
2015-06-28
期刊：
影响因子：
9.7
通讯作者：
Liu, Gang
中科院分区：
文献类型：
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作者：
Huang, Haili;Jiang, Yun;Liu, Gang
我们先前的研究表明，microRNA 5100（miR-5100）在肺癌组织中过表达;然而，miR-5100的功能仍然难以捉摸。在这项研究中，我们证明了miR-5100在多种肺癌组织和肺癌细胞系中高度表达。外源性表达miR-5100可促进A549和H1299肺癌细胞的增殖和集落形成，反之，抑制miR-5100则表现出抑制作用。此外，我们证明了miR-5100促进裸鼠肿瘤生长。这些作用可能是由于miR-5100能够促进肺癌稳定细胞的G1/S转换并下调细胞周期蛋白D1和细胞周期蛋白依赖性激酶2（CDK 2）的表达。使用生物信息学靶标预测工具，我们将Rab 6鉴定为miR-5100的潜在靶标。一致地，miR-5100的过表达特异性地降低了含有来自Rab 6的3 '非翻译区（3' UTR）的预测结合位点的荧光素酶报告基因的表达，并降低了内源性Rab 6在A549和H1299细胞中的积累。此外，Rab 6的外源性表达损害了miR-5100对细胞增殖和集落形成的作用。我们的数据表明，miR-5100通过促进G1/S转换和靶向Rab 6促进肿瘤生长。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Our previous study demonstrated that microRNA 5100 (miR-5100) is overexpressed in lung cancer tissues; however, the function of miR-5100 remained elusive. In this study, we demonstrate that miR-5100 is highly expressed in a wide variety of lung cancer tissues and lung cancer cell lines. Exogenous expression of miR-5100 in A549 and H1299 lung cancer cells enhanced proliferation and colony formation, and conversely, suppression of miR-5100 exhibited inhibitory effects. Furthermore, we demonstrate that miR-5100 promotes tumor growth in nude mice. These effects may result from the ability of miR-5100 to promote G1/S transition and downregulate cyclin D1 and cyclin-dependent kinases 2 (CDK2) expressions in lung cancer stable cells. Using a bioinformatics target prediction tool, we identified Rab6 as a potential target of miR-5100. Consistently, overexpression of miR-5100 specifically reduced the expression of a luciferase reporter containing the predicted binding site from the 3'untranslated region (3'UTR) of Rab6 and decreased the accumulation of endogenous Rab6 in A549 and H1299 cells. Moreover, exogenous expression of Rab6 compromised the effects of miR-5100 on cell proliferation and colony formation. Our data suggest that miR-5100 promotes tumor growth by facilitating the G1/S transition and targeting Rab6. (C) 2015 Elsevier Ireland Ltd. All rights reserved.