miR-495 and miR-551a inhibit the migration and invasion of human gastric cancer cells by directly interacting with PRL-3
miR-495 and miR-551a inhibit the migration and invasion of human gastric cancer cells by directly interacting with PRL-3
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miR-495和miR-551a通过直接与PRL-3相互作用抑制人胃癌细胞的迁移和侵袭
DOI：
10.1016/j.canlet.2012.03.029
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发表时间：
2012-10-01
期刊：
影响因子：
9.7
通讯作者：
Park, Sung-soo
中科院分区：
文献类型：
--
作者：
Li, Zhengrong;Cao, Yi;Park, Sung-soo
肝再生磷酸酶-3（PRL-3）基因与胃癌的转移有关，并被认为通过促进肿瘤细胞的运动、侵袭和转移而发挥致病作用，但其机制尚不清楚。我们以前报道过PRL-3在原发性胃癌腹膜转移组织中的表达显著增高。在本研究中，我们发现两个microRNAs（miRNAs），miR-495和miR-551 a，预测目标PRL-3，在胃癌样品中下调。在用miR-495和miR-551 a模拟物转染的GC细胞系中，通过蛋白质印迹和定量实时PCR（qPCR）证实了这两种miRNA与PRL-3之间的这种相互作用的验证。此外，miR-495或-551a模拟物转染可显著抑制胃癌细胞的迁移和侵袭，并降低过表达miR-495或-551a的胃癌细胞中PRL-3的mRNA和蛋白水平。总的来说，我们的研究结果表明，miR-495和miR-551 a都作为肿瘤抑制因子，通过靶向PRL-3癌基因，抑制胃癌细胞的迁移和侵袭。本研究的发现有助于目前了解的功能，miRNA模拟物在GC基因治疗。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
The phosphatase of regenerating liver-3 (PRL-3) gene is associated with metastasis in gastric cancer, and is believed to play a causative role by promoting tumor cell motility, invasion, and metastasis, but little is known of the mechanisms involved. We previously reported that PRL-3 expression is significantly higher in the tissues of primary gastric carcinomas with peritoneal metastasis. In the present study, we found that two microRNAs (miRNAs), miR-495 and miR-551a, predicted to target PRL-3, are downregulated in gastric carcinoma samples. The validation of this interaction between those two miRNAs and PRL-3 was confirmed by western blotting and quantitative real-time PCR (qPCR) in GC cell lines transfected with miR-495 and miR-551a mimics. Furthermore, the migration and invasion of GC cells were significantly inhibited by transfection with miR-495 or -551a mimics, and the mRNA and protein levels of PRL-3 were reduced in cells overexpressing miR-495 or -551a. Collectively, our findings suggest that miR-495 and miR-551a both act as tumor suppressors by targeting the PRL-3 oncogene and inhibiting gastric cancer cell migration and invasion. The findings of this study contribute to current understanding of the functions of miRNA mimics in GC gene therapy. (C) 2012 Elsevier Ireland Ltd. All rights reserved.