MicroRNA-122 triggers mesenchymal-epithelial transition and suppresses hepatocellular carcinoma cell motility and invasion by targeting RhoA.
MicroRNA-122 triggers mesenchymal-epithelial transition and suppresses hepatocellular carcinoma cell motility and invasion by targeting RhoA.
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MicroRNA-122 通过靶向 RhoA 触发间质-上皮转化并抑制肝细胞癌细胞运动和侵袭
DOI：
10.1371/journal.pone.0101330
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Xiao D
中科院分区：
文献类型：
--
作者：
Wang SC;Lin XL;Li J;Zhang TT;Wang HY;Shi JW;Yang S;Zhao WT;Xie RY;Wei F;Qin YJ;Chen L;Yang J;Yao KT;Xiao D
The loss of microRNA-122 (miR-122) expression is strongly associated with increased invasion and metastasis, and poor prognosis of hepatocellular carcinoma (HCC), however, the underlying mechanisms remain poorly understood. In the present study, we observed that miR-122 over-expression in HCC cell lines Sk-hep-1 and Bel-7402 triggered the mesenchymal-epithelial transition (MET), as demonstrated by epithelial-like morphological changes, up-regulated epithelial proteins (E-cadherin, ZO-1, α-catenin, occludin, BVES, and MST4), and down-regulated mesenchymal proteins (vimentin and fibronectin). The over-expression of miRNA-122 also caused cytoskeleton disruption, RhoA/Rock pathway inactivation, enhanced cell adhesion, and suppression of migration and invasion of Sk-hep-1 and Bel-7402 cells, whereas, these effects could be reversed through miR-122 inhibition. Additional studies demonstrated that the inhibition of wild-type RhoA function induced MET and inhibited cell migration and invasion, while RhoA over-expression reversed miR-122-induced MET and inhibition of migration and invasion of HCC cells, suggesting that miR-122 induced MET and suppressed the migration and invasion of HCC cells by targeting RhoA. Moreover, our results demonstrated that HNF4α up-regulated its target gene miR-122 that subsequently induced MET and inhibited cell migration and invasion, whereas miR-122 inhibition reversed these HNF4α-induced phenotypes. These results revealed functional and mechanistic links among the tumor suppressors HNF4α, miR-122, and RhoA in EMT and invasive and metastatic phenotypes of HCC. Taken together, our study provides the first evidence that the HNF4α/miR-122/RhoA axis negatively regulates EMT and the migration and invasion of HCC cells.
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影响因子：
25.7
作者：
Li, Jiang;Ghazwani, Mohammed;Zhang, Yifei;Lu, Jianqin;Li, Jilong;Fan, Jie;Gandhi, Chandrashekhar R.;Li, Song
通讯作者：
Li, Song
影响因子：
25.7
作者：
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通讯作者：
Liang, Chih-Chuan
影响因子：
3.9
作者：
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通讯作者：
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影响因子：
4
作者：
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通讯作者：
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影响因子：
29.4
作者：
Liang, Li;Li, Xianzheng;Ding, Yanqing
通讯作者：
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