LAUSR

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.