Downregulation of Human Farnesoid X Receptor by miR-421 Promotes Proliferation and Migration of Hepatocellular Carcinoma Cells
Downregulation of Human Farnesoid X Receptor by miR-421 Promotes Proliferation and Migration of Hepatocellular Carcinoma Cells
复制标题
miR-421下调人法尼醇X受体促进肝细胞癌细胞的增殖和迁移
DOI：
10.1158/1541-7786.mcr-11-0473
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发表时间：
2012-04-01
影响因子：
5.2
通讯作者：
He, Fengtian
中科院分区：
文献类型：
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作者：
Zhang, Yan;Gong, Wei;He, Fengtian
法尼醇X受体（FXR）是核受体超家族的成员，其在肝、肾、肾上腺和肠中高度表达。它在调节包括肝细胞癌（HCC）在内的几种癌症的进展中起重要作用。因此，有必要对FXR的调控进行研究。在本研究中，我们发现miR-421的表达与HCC细胞系中FXR蛋白水平呈负相关。用miR-421模拟物处理抑制FXR翻译。报告基因检测显示miR-421靶向于人FXR mRNA的3′非翻译区。此外，miR-421下调FXR可促进HCC细胞的增殖、迁移和侵袭。这些结果表明，miR-421可能作为一个新的分子靶点，操纵肝细胞中的FXR表达和治疗HCC。Mol Cancer Res; 10（4）; 516-22.©2012 AACR。
The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidney, adrenal gland, and intestine. It plays an important role in regulating the progression of several cancers including hepatocellular carcinoma (HCC). So it is necessary to study the regulation of FXR. In this study, we found that the expression of miR-421 was inversely correlated with FXR protein level in HCC cell lines. Treatment with miR-421 mimic repressed FXR translation. The reporter assay revealed that miR-421 targeted 3′ untranslated region of human FXR mRNA. Furthermore, downregulation of FXR by miR-421 promoted the proliferation, migration, and invasion of HCC cells. These results suggest that miR-421 may serve as a novel molecular target for manipulating FXR expression in hepatocyte and for the treatment of HCC. Mol Cancer Res; 10(4); 516–22. ©2012 AACR.