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微小RNA-497通过靶向血管内皮生长因子-A抑制结肠癌细胞的侵袭和转移。

microRNA-497 inhibits invasion and metastasis of colorectal cancer cells by targeting vascular endothelial growth factor-A.

作者信息

Qiu Yanyan, Yu Hui, Shi Xiaojing, Xu Ke, Tang Qingfeng, Liang Bo, Hu Songjiao, Bao Yijie, Xu Jianhua, Cai Jie, Peng Wen, Cao Qin, Yin Peihao

机构信息

Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.

Cancer Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.

出版信息

Cell Prolif. 2016 Feb;49(1):69-78. doi: 10.1111/cpr.12237. Epub 2016 Feb 3.

Abstract

OBJECTIVES

microRNAs (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 METHODS

RT-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.

RESULTS

miR-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.

CONCLUSIONS

Thus 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.

摘要

目的

微小RNA(miRNA)是一类调控基因表达的非编码RNA,参与肿瘤的发生发展。本研究旨在探讨微小RNA - 497(miR - 497)在结直肠癌(CRC)发生发展中的表达及其作用。

材料与方法

采用逆转录聚合酶链反应(RT - PCR)检测miR - 497在结直肠癌细胞系(HCT8、LOVO、Ls - 174、HCT116和HT29)及临床癌症标本中的表达。为进一步了解其作用,通过转染miR - 497模拟物或抑制剂在HCT116细胞系中恢复miR - 497的表达。还在体外和体内确定了miR - 497对靶细胞增殖、迁移和侵袭的影响。

结果

与非肿瘤组织及肿瘤细胞系相比,34例结直肠癌组织中miR - 497表达降低。miR - 497的过表达并未抑制癌细胞生长,但在体外和体内均抑制了转移和侵袭。血管内皮生长因子 - A(VEGF - A)被证实是miR - 497的一个靶标。此外,我们发现miR - 497的过表达改变了VEGF - A/ERK/MMP - 9信号通路关键分子的表达。

结论

因此,我们的结果提供了证据表明miR - 497可能在结直肠癌中作为一种转移抑制因子发挥作用。靶向miR - 497可能为阻断其转移提供一种策略。

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