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miR-194 是肝上皮细胞的标志物,可抑制肝癌细胞在小鼠中的转移。

miR-194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice.

机构信息

Division of Gene Regulation and Drug Discovery, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.

出版信息

Hepatology. 2010 Dec;52(6):2148-57. doi: 10.1002/hep.23915. Epub 2010 Oct 26.

Abstract

UNLABELLED

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by interacting with the 3' untranslated region (3'-UTR) of multiple mRNAs. Recent studies have linked miRNAs to the development of cancer metastasis. In this study, we show that miR-194 is specifically expressed in the human gastrointestinal tract and kidney. Moreover, miR-194 is highly expressed in hepatic epithelial cells, but not in Kupffer cells or hepatic stellate cells, two types of mesenchymal cells in the liver. miR-194 expression was decreased in hepatocytes cultured in vitro, which had undergone a dedifferentiation process. Furthermore, expression of miR-194 was low in liver mesenchymal-like cancer cell lines. The overexpression of miR-194 in liver mesenchymal-like cancer cells reduced the expression of the mesenchymal cell marker N-cadherin and suppressed invasion and migration of the mesenchymal-like cancer cells both in vitro and in vivo. We further demonstrated that miR-194 targeted the 3'-UTRs of several genes that were involved in epithelial-mesenchymal transition and cancer metastasis.

CONCLUSION

These results support a role of miR-194, which is specifically expressed in liver parenchymal cells, in preventing liver cancer cell metastasis.

摘要

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微小 RNA(miRNAs)是一种小型非编码 RNA,通过与多个 mRNA 的 3'非翻译区(3'-UTR)相互作用来调节基因表达。最近的研究将 miRNAs 与癌症转移的发展联系起来。在这项研究中,我们表明 miR-194 特异性表达于人类胃肠道和肾脏。此外,miR-194 在肝上皮细胞中高度表达,但在库普弗细胞或肝星状细胞中不表达,肝星状细胞是肝脏中的两种间质细胞。体外培养的肝细胞发生去分化过程时,miR-194 的表达减少。此外,miR-194 在肝间充质样癌细胞系中的表达水平较低。在肝间充质样癌细胞中过表达 miR-194 可降低间充质细胞标志物 N-钙黏蛋白的表达,并抑制间充质样癌细胞在体外和体内的侵袭和迁移。我们进一步证明 miR-194 靶向参与上皮-间充质转化和癌症转移的几个基因的 3'-UTRs。

结论

这些结果支持 miR-194 的作用,miR-194 特异性表达于肝实质细胞,可防止肝癌细胞转移。

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