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首页> 外文期刊>OncoTargets and therapy >MicroRNA-29a plays a suppressive role in non-small cell lung cancer cells via targeting LASP1
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MicroRNA-29a plays a suppressive role in non-small cell lung cancer cells via targeting LASP1

机译:MicroRNA-29a通过靶向LASP1在非小细胞肺癌细胞中起抑制作用

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摘要

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.
机译:MicroRNA(miR)-29a与非小细胞肺癌(NSCLC)有关,但其机制仍不清楚。最近发现,LASP1是一种cAMP和cGMP依赖性信号蛋白,可促进NSCLC的增殖和侵袭性。但是,以前从未研究过NSCLC中LASP1表达的调控机制以及LASP1与miR-29a之间的关系。在这项研究中,我们发现miR-29a明显下调,miR-29a的低表达与NSCLC的恶性进展有关。此外,LASP1的表达在非小细胞肺癌组织和细胞系中明显增加。生物信息学分析和萤光素酶报告基因检测数据进一步确定LASP1是miR-29a的靶基因,并且在转录后水平,NSCLC细胞中miR-29a负调控LASP1的表达。就像LASP1敲除的作用一样,miR-29a的过表达减少了NSCLC细胞的增殖,迁移和侵袭。此外,LASP1的过表达减弱了miR-29a对NSCLC细胞恶性表型的抑制作用。另外,miR-29a的上调减少了裸鼠中A549细胞的生长,并保护了这些动物免于肿瘤引起的死亡。因此,我们证明miR-29a通过靶向LASP1在NSCLC中起抑制作用,提示miR-29a / LASP1轴可能成为NSCLC的有希望的治疗靶标。

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