期刊
INTERNATIONAL JOURNAL OF CANCER
卷 142, 期 3, 页码 547-560出版社
WILEY
DOI: 10.1002/ijc.31050
关键词
clear cell renal cell carcinoma; microRNA; Dicer; prognosis; metastasis; migration; invasion; epithelial-mesenchymal transition
类别
资金
- National High Technology Research and Development Program of China [2012AA02101, 2014AA020607]
- National Natural Science Foundation of China [81402109]
- Chenguang Program of Wuhan Science and Technology Bureau [2013072304010833]
- Natural Science Foundation of Hubei Province [2015CFB289]
Although overall downregulation of microRNAs (miRNAs) is a general feature of clear-cell renal cell carcinoma (ccRCC), several miRNAs are consistently upregulated, among which miR-122 was markedly increased in ccRCC tissues. Our study aims to determine the functional importance and underlying mechanism of miR-122 in ccRCC metastasis. Here, we demonstrate that the expression of miR-122 increased in ccRCC tissues, and higher miR-122 expression was found in ccRCC tissues with metastatic disease than in those without metastasis. The increased miR-122 levels were associated with poor metastasis-free survival in ccRCC patients with localized disease. Dicer was validated as a direct functional target of miR-122. Overexpression of miR-122 promoted migration and invasion of ccRCC cells in vitro and metastatic behavior of ccRCC cells in vivo. Inhibition of miR-122 attenuated this metastatic phenotype in vitro. Importantly, miR-122 exerted its pro-metastatic properties in ccRCC cells by downregulating Dicer and its downstream effector, the miR-200 family, thereby inducing epithelial-mesenchymal transition (EMT). Our results suggest an important role of the miR-122/Dicer/miR-200s/EMT pathway in ccRCC metastasis. Furthermore, miR-122 may serve as a biomarker for discriminating ccRCC with metastatic potential.
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