MiR-155 up-regulated by TGF-β promotes epithelial-mesenchymal transition, invasion and metastasis of human hepatocellular carcinoma cells in vitro.

It has previously been reported that microRNA (miR)-155 is linked to the recurrence and prognosis of hepatocellular carcinoma (HCC) following liver transplantation. However, the role of miR-155 in the invasion and metastasis of HCC cells remains largely unclear. The aim of this study was to investigate the expression of miR-155 in HCC cells and its role in the invasion and migration of HCC cells in vitro. We found that the level of expression of miR-155 in HCC tissues and cells was significantly increased compared with non-tumorous adjacent tissues. Further study revealed that recombinant human transforming growth factor-β (TGF-β1) up-regulated the expression of miR-155 in HCC cells in vitro. Further, the overexpression of miR-155 in HCC cell line Huh-7 led to increased levels of cell invasion and migration compared with untreated control Huh-7 cells. MiR-155-overexpressed Huh-7 cells also exhibited altered levels of expression of certain cellular adhesion molecules related to epithelial-mesenchymal transition (EMT), including low levels of CDH1 and higher levels of FN1, SNAI1 and ZEB1, compared with control Huh-7 cells. Moreover, it was found that the overexpression of miR-155 and of TGF-β1 protein decreased the expression of E-Cadherin and increased the expression of Vimentin in Huh-7 cells. These results indicate that an increased level of miR-155 in HCC cells, possibly due to stimulation by TGF-β1, accelerates the process of EMT, promotes cellular invasion and migration in vitro, and thereby further promotes the progression of HCC.