MicroRNA-29a plays a suppressive role in non-small cell lung cancer cells via targeting LASP1.
MicroRNA-29a plays a suppressive role in non-small cell lung cancer cells via targeting LASP1.
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MicroRNA-29a 通过靶向 LASP1 在非小细胞肺癌细胞中发挥抑制作用。
DOI：
10.2147/ott.s116509
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发表时间：
2016
影响因子：
4
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Hu Z;Cui Y;Zhou Y;Zhou K;Qiao X;Li C;Wang S
microRNA（miR）-29a与非小细胞肺癌（NSCLC）有关，但其机制尚不清楚。LASP 1是一种cAMP和cGMP依赖性信号蛋白，最近发现可促进NSCLC的增殖和侵袭性。然而，LASP 1在NSCLC中表达的调控机制，以及LASP 1与miR-29 a之间的关系，以前从未被研究过。在本研究中，我们发现miR-29 a显著下调，并且miR-29 a的低表达与NSCLC的恶性进展相关。LASP 1在NSCLC组织和细胞系中的表达明显增加。生物信息学分析和荧光素酶报告基因分析数据进一步确定LASP 1为miR-29 a的靶基因，并且LASP 1在NSCLC细胞中的表达由miR-29 a在转录后水平负介导。miR-29 a的过表达降低了NSCLC细胞的增殖、迁移和侵袭能力，与LASP 1基因敲低的作用相同。此外，LASP 1的过表达减弱了miR-29 a对NSCLC细胞恶性表型的抑制作用。此外，miR-29 a的上调降低了裸鼠中A549细胞的生长，并保护动物免于肿瘤诱导的死亡。因此，我们证明miR-29 a通过靶向LASP 1在NSCLC中发挥抑制作用，表明miR-29 a/LASP 1轴可能成为NSCLC的有希望的治疗靶点。
MicroRNA (miR)-29a has been implicated in non-small cell lung cancer (NSCLC), but the mechanism remains largely unclear. LASP1, a cAMP- and cGMP-dependent signaling protein, was recently found to promote proliferation and aggressiveness in NSCLC. However, the regulatory mechanism of LASP1 expression in NSCLC, as well as the relationship between LASP1 and miR-29a, has never been previously studied. In this study, we found that miR-29a was remarkably downregulated and low expression of miR-29a was associated with the malignant progression of NSCLC. Moreover, the expression of LASP1 was markedly increased in NSCLC tissues and cell lines. Bioinformatics analysis and luciferase reporter assay data further identified LASP1 as a target gene of miR-29a, and the expression of LASP1 was negatively mediated by miR-29a at the post-transcriptional level in NSCLC cells. Overexpression of miR-29a reduced the proliferation, migration, and invasion of NSCLC cells, just as the effects of LASP1 knockdown. Moreover, overexpression of LASP1 attenuated the suppressive effect of miR-29a on the malignant phenotypes of NSCLC cells. In addition, upregulation of miR-29a decreased the growth of A549 cells in nude mice and protected the animals from tumor-induced death. Therefore, we demonstrate that miR-29a plays a suppressive role in NSCLC via targeting LASP1, suggesting that the miR-29a/LASP1 axis may become a promising therapeutic target for NSCLC.