miR-340 inhibition of breast cancer cell migration and invasion through targeting of oncoprotein c-Met

Zheng-sheng Wu, Qiang Wu, Chao-qun Wang, Xiao-nan Wang, Jing Huang, Jing-jing Zhao, Shan-shan Mao, Gui-hong Zhang, Xiao-chun Xu, Nong Zhang
Cancer 2011 July 1, 117 (13): 2842-52

BACKGROUND: Different microRNAs have been shown to have oncogenic and tumor-suppressive functions in human cancers. Detection of their expression may lead to identifying novel markers for breast cancer.

METHODS: The authors detected miR-340 expression in 4 human breast cell lines and then focused on its role in regulation of tumor cell growth, migration, and invasion and target gene expression. They then analyzed miR-340 expression in benign and cancerous breast tissue specimens.

RESULTS: Endogenous miR-340 expression was down-regulated in the more aggressive breast cancer cell lines, which was confirmed in breast cancer tissue specimens by using quantitative real-time polymerase chain reaction. Further studies showed that induction of miR-340 expression was able to suppress tumor cell migration and invasion, whereas knockdown of miR-340 expression induced breast cancer cell migration and invasion. At the gene level, the authors identified c-Met as a direct miR-340 target to mediate cell migration and invasion through regulation of MMP-2 and MMP-9 expression. Ex vivo, loss of miR-340 expression was associated with lymph node metastasis, high tumor histological grade, clinical stage, and shorter overall survival of breast cancer as well as increased c-Met expression in breast cancer tissue specimens.

CONCLUSIONS: miR-340 may play an important role in breast cancer progression, suggesting that miR-340 should be further evaluated as a novel biomarker for breast cancer metastasis and prognosis, and potentially a therapeutic target.

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