MiR-153 inhibits migration and invasion of human non-small-cell lung cancer by targeting ADAM19
MiR-153 inhibits migration and invasion of human non-small-cell lung cancer by targeting ADAM19
复制标题
DOI：
10.1016/j.bbrc.2014.11.093
复制
发表时间：
2015-01-02
影响因子：
3.1
通讯作者：
Duan, Chaojun
中科院分区：
文献类型：
--
作者：
Shan, Nianxi;Shen, Liangfang;Duan, Chaojun
据报道，miR-153在一些人类癌症中失调。然而，miR-153在肺癌细胞中的功能和机制仍不清楚。在这项研究中，我们研究了miR-153在人类非小细胞肺癌（NSCLC）中的作用。使用qRT-PCR，我们证明miR-153在临床NSCLC组织和细胞系中显著降低，并且miR-153的下调与淋巴结状态显著相关。我们进一步发现miR-153的异位表达在体外显著抑制NSCLC细胞的增殖、迁移和侵袭，提示miR-153可能是NSCLC中一种新的肿瘤抑制因子。进一步的综合分析表明，ADAM 19是miR-153的直接功能靶点。荧光素酶报告基因检测显示miR-153直接靶向于ADAM 19的3 'UTR，相关性分析显示miR-153与ADAM 19 mRNA在临床NSCLC组织中的表达水平呈负相关。敲低ADAM 19可抑制NSCLC细胞的迁移和侵袭，其作用与过表达miR-153相似，而过表达ADAM 19可减弱miR-153在NSCLC细胞中的功能。综上所述，我们的结果强调了miR-153和ADAM 19在NSCLC发生和进展中的重要性。(C)2014爱思唯尔公司All rights reserved.
MiR-153 was reported to be dysregulated in some human cancers. However, the function and mechanism of miR-153 in lung cancer cells remains unknown. In this study, we investigated the role of miR-153 in human non-small-cell lung cancer (NSCLC). Using qRT-PCR, we demonstrated that miR-153 was significantly decreased in clinical NSCLC tissues and cell lines, and downregulation of miR-153 was significantly correlated with lymph node status. We further found that ectopic expression of miR-153 significantly inhibited the proliferation and migration and invasion of NSCLC cells in vitro, suggesting that miR-153 may be a novel tumor suppressor in NSCLC. Further integrated analysis revealed that ADAM19 is as a direct and functional target of miR-153. Luciferase reporter assay demonstrated that miR-153 directly targeted 3'UTR of ADAM19, and correlation analysis revealed an inverse correlation between miR-153 and ADAM19 mRNA levels in clinical NSCLC tissues. Knockdown of ADAM19 inhibited migration and invasion of NSCLC cells which was similar with effects of overexpression of miR-153, while overexpression of ADAM19 attenuated the function of miR-153 in NSCLC cells. Taken together, our results highlight the significance of miR-153 and ADAM19 in the development and progression of NSCLC. (C) 2014 Elsevier Inc. All rights reserved.