Although the high expression of miR-194 in the liver has been known for a long time, its function is poorly understood. Two studies on intestinal
epithelial cell differentiation and liver fibrogenesis have shed light on the function of miR-194.14, 15 Because both processes involved interaction or conversion between epithelial cells and mesenchymal cells, we hypothesize that miR-194 may be specifically expressed in liver epithelial cells and is down-regulated during a dedifferentiation process mimicking EMT. Indeed, we demonstrated that miR-194 was highly expressed in hepatic epithelial cells but not in mesenchymal-like cells. We further determined that one potential role of miR-194 in epithelial cells was to suppress N-cadherin expression and hinder the cadherin switch during EMT. Overexpression selleck screening library of miR-194 in the mesenchymal-like liver cancer cell lines decreased N-cadherin expression and suppressed cell migration, invasion, and metastasis. Moreover, miR-194 reversed the loss of the epithelial cell marker E-cadherin in a mesenchymal cell line, SNU475. This indicates that the miR-194 overexpression might reverse the status of cell differentiation in certain cellular contexts probably by releasing the transcriptional or translational repression on E-cadherin in mesenchymal cells. Although these results are not conclusive, they SAR245409 reveal a potential role of miR-194
in maintaining the epithelial phenotypes of the cells and preventing EMT during cancer progression. Only a few miRNAs have been reported to be involved in EMT. Gregory et al.5showed that all five members of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141,
and miR-429) selleckchem and miR-205 were down-regulated in cells that underwent EMT. Ectopic expression of miR-200 family members in mesenchymal cells initiated a mesenchymal-to-epithelial transition process by reducing the expression of ZEB1 and ZEB2, the most important transcription repressors of E-cadherin, by targeting their 3′-UTRs. It has been further suggested that miR-200 can suppress migration and metastasis of cancer cells. However, beyond the miR-200 family and miR-205, only a few reports have investigated the role of miRNAs in both EMT and metastasis, although several studies have identified their potential roles in regulating metastasis.39 Our results indicate that miR-194 may specifically suppress N-cadherin expression but does not have strong effects on E-cadherin expression. In clinical scenarios, metastatic cells do not always undergo a full EMT, because E-cadherin is not lost in many metastatic cancers.40 In addition, though the loss of E-cadherin was regarded as a hallmark of EMT, the subsequently increased expression of N-cadherin and vimentin might be necessary to promote EMT by enhancing migration and metastasis of cancer cells.