Division of Gene Regulation and Drug Discovery, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
Hepatology. 2010 Dec;52(6):2148-57. doi: 10.1002/hep.23915. Epub 2010 Oct 26.
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.
These results support a role of miR-194, which is specifically expressed in liver parenchymal cells, in preventing liver cancer cell metastasis.
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。
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。
