miR-122 promotes metastasis of clear-cell renal cell carcinoma by downregulating Dicer
miR-122 promotes metastasis of clear-cell renal cell carcinoma by downregulating Dicer
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miR-122通过下调Dicer促进透明细胞肾细胞癌的转移
DOI：
10.1002/ijc.31050
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发表时间：
2018-02-01
影响因子：
6.4
通讯作者：
Zhang, Xu
中科院分区：
文献类型：
--
作者：
Fan, Yang;Ma, Xin;Zhang, Xu
尽管微小RNA（miRNAs）的总体下调是透明细胞肾细胞癌（ccRCC）的一般特征，但几种miRNAs持续上调，其中miR-122在ccRCC组织中显著增加。我们的研究旨在确定miR-122在ccRCC转移中的功能重要性和潜在机制。在这里，我们证明了miR-122在ccRCC组织中的表达增加，并且在具有转移性疾病的ccRCC组织中发现了比没有转移的那些更高的miR-122表达。miR-122水平的增加与局部疾病的ccRCC患者的无转移生存率相关。Dicer被验证为miR-122的直接功能靶标。miR-122的过表达促进了ccRCC细胞的体外迁移和侵袭以及ccRCC细胞的体内转移行为。miR-122的抑制在体外减弱了这种转移表型。重要的是，miR-122通过下调Dicer及其下游效应物miR-200家族在ccRCC细胞中发挥其促转移特性，从而诱导上皮-间质转化（EMT）。我们的研究结果表明miR-122/Dicer/miR-200 s/EMT通路在ccRCC转移中的重要作用。此外，miR-122可作为鉴别具有转移潜能的ccRCC的生物标志物。
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.