microRNA-497 inhibits invasion and metastasis of colorectal cancer cells by targeting vascular endothelial growth factor-A
microRNA-497 inhibits invasion and metastasis of colorectal cancer cells by targeting vascular endothelial growth factor-A
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microRNA-497通过靶向血管内皮生长因子-A抑制结直肠癌细胞的侵袭和转移
DOI：
10.1111/cpr.12237
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发表时间：
2016-02-01
影响因子：
8.5
通讯作者：
Yin, Peihao
中科院分区：
文献类型：
--
作者：
Qiu, Yanyan;Yu, Hui;Yin, Peihao
目的microRNAs(MiRNAs)是调控基因表达的非编码RNA，与肿瘤的发生发展密切相关。本研究旨在探讨microRNA-497(miR-497)的表达及其在结直肠癌发生发展中的作用。材料与方法采用RT-PCR方法检测miR-497在结直肠癌细胞系(HCT8、LOVO、LS-174、HCT116和HT29)及临床癌组织中的表达。为了进一步了解miR-497的作用，我们通过转染miR-497模拟物或抑制剂恢复了miR-497在HCT116细胞中的表达。结果在34例大肠癌组织中，miR-497的表达明显低于非肿瘤组织和肿瘤细胞系。MiR-497的过表达不能抑制癌细胞的生长，但在体内和体外都能抑制肿瘤的转移和侵袭。血管内皮生长因子-A(VEGF-A)被证实是miR-497的靶点。此外，我们还发现miR-497过表达改变了血管内皮生长因子-A/ERK/基质金属蛋白酶-9信号通路的关键分子的表达。靶向miR-497可能为阻断其转移提供了一种策略。
ObjectivesmicroRNAs (miRNAs), are non-coding RNAs that regulate gene expression, and are involved in tumour development. The aim of this study was to investigate microRNA-497 (miR-497) expression and its role in development of colorectal cancer (CRC).Materials and methodsRT-PCR was performed to detect expression of miR-497 in CRC cell lines (HCT8, LOVO, Ls-174, HCT116 and HT29) and in clinical cancer specimens. To further understand its role, we restored expression of miR-497 in the HCT116 cell line by transfection with miR-497 mimics or inhibitors. Effects of miR-497 on cell proliferation, migration and invasion of targets were also determined both in vitro and in vivo.ResultsmiR-497 expression decreased in 34 CRC tissues compared to non-tumour tissues and in tumour cell lines. Overexpression of miR-497 did not inhibit cancer cell growth but suppressed metastasis and invasion both in vitro and in vivo. Vascular endothelial growth factor-A (VEGF-A) was confirmed to be a target of miR-497. Furthermore, we found overexpression of miR-497 altered expression of key molecules of the VEGF-A/ERK/MMP-9 signalling pathway.ConclusionsThus our results provide evidence that miR-497 might function as a metastasis suppressor in CRC. Targeting miR-497 may provide a strategy for blocking its metastasis.