Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Hubei Provincial Key Laboratory of Allergy and Immune-Related Diseases and Center for Medical Research, Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, PR China.
Eur J Cancer. 2012 Aug;48(12):1904-13. doi: 10.1016/j.ejca.2011.11.026. Epub 2011 Dec 19.
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.
血管扩张刺激磷蛋白(VASP)已被牵涉到癌症表型的建立中。然而,VASP 在胃癌进展和转移中的作用仍知之甚少。在这里,我们证明了 VASP 被表皮生长因子(EGF)上调,并促进了胃癌细胞的迁移和侵袭。然后,我们探讨了导致胃癌中 VASP 高表达的调节机制。基于配对胃癌组织及其相邻非肿瘤胃组织的 miRNA 表达谱分析,我们鉴定了包括 microRNA-610(miR-610)在内的 18 个 miRNA 在胃癌中下调。接下来,我们观察到 EGF 刺激后胃癌细胞中 VASP 和 miR-610 表达水平之间存在反比关系。然后,我们进行了生物信息学分析、Western blot 和逆转录聚合酶链反应(RT-PCR)分析和荧光素酶测定,以确定 miR-610 直接靶向 VASP 3'-UTR 并抑制其表达。功能上,我们证明了 miR610 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。鉴定出 miR-610 是一种受 EGF 调控的新型 miRNA,可靶向胃癌细胞中的 VASP,表明 EGF-miR610-VASP 轴可能被用于治疗干预以抑制胃癌的进展和转移。