MicroRNA-610 inhibits the migration and invasion of gastric cancer cells by suppressing the expression of vasodilator-stimulated phosphoprotein
MicroRNA-610 inhibits the migration and invasion of gastric cancer cells by suppressing the expression of vasodilator-stimulated phosphoprotein
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MicroRNA-610通过抑制血管舒张刺激磷蛋白的表达抑制胃癌细胞的迁移和侵袭
DOI：
10.1016/j.ejca.2011.11.026
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发表时间：
2012-08-01
影响因子：
8.4
通讯作者：
Wei, Lei
中科院分区：
文献类型：
--
作者：
Wang, Jing;Zhang, Jingwei;Wei, Lei
血管舒张刺激磷蛋白（VASP）已被牵连在建立癌表型。然而，VASP在胃癌进展和转移中的作用仍然知之甚少。在这里，我们证明了VASP被表皮生长因子（EGF）上调，并促进胃癌细胞的迁移和侵袭。探讨VASP在胃癌中高表达的调控机制。根据配对胃癌组织及其邻近非肿瘤胃组织的miRNA表达谱，鉴定了18种miRNA，包括在胃癌中下调的microRNA-610（miR-610）。接下来，我们观察到EGF刺激后胃癌细胞中VASP和miR-610表达水平之间的负相关性。通过生物信息学分析、Western blot和RT-PCR分析以及荧光素酶检测，证实miR-610直接靶向VASP 3 '-UTR并抑制其表达。在功能上，我们证明了miR 610介导的VASP表达抑制导致胃癌细胞迁移和侵袭特性的显著降低。miR-610是一种由EGF调控的靶向胃癌细胞中VASP的新型miRNA，这表明EGF-miR-610-VASP轴可用于抑制胃癌进展和转移的治疗干预。(C)2011爱思唯尔有限公司保留所有权利。
Vasodilator-stimulated phosphoprotein (VASP) has been implicated in the establishment of cancerous phenotypes. However, the role of VASP in gastric cancer progression and metastasis remains poorly understood. Here, we demonstrated that VASP was upregulated by epidermal growth factor (EGF) and promoted the migration and invasion of gastric cancer cells. Then we explored the regulatory mechanisms responsible for high expression of VASP in gastric cancer. Based on miRNA expression profiling of the paired gastric cancer tissues and their adjacent non-tumour gastric tissues 18 miRNAs were identified including microRNA-610 (miR-610) which were down-regulated in gastric cancer. Next, we observed an inverse correlation between VASP and miR-610 expression levels in gastric cancer cells after EGF stimulation. Then we performed bioinformatics analysis, Western blot and reverse transcription polymerase chain reaction (RT-PCR) analysis and luciferase assay to establish that miR-610 directly targets VASP 3'-UTR and inhibits its expression. Functionally, we demonstrated that miR610-mediated inhibition of VASP expression resulted in a significant reduction in the migration and invasion properties of gastric cancer cells. The identification of miR-610 as a novel miRNA regulated by EGF that targets VASP in gastric cancer cells suggests that EGF-miR610-VASP axis may be exploited for therapeutic intervention to inhibit gastric cancer progression and metastasis. (C) 2011 Elsevier Ltd. All rights reserved.