MicroRNA-101 inhibits the migration and invasion of intrahepatic cholangiocarcinoma cells via direct suppression of vascular endothelial growth factor-C

Abstract

MicroRNAs (miRs) have important roles in the pathogenesis of human malignancy. It has previously been suggested that deregulation of miR-101 is associated with the progression of intrahepatic cholangiocarcinoma (ICC); however, the exact role of miR-101 in the regulation of ICC metastasis remains largely unknown. The present study demonstrated that the expression levels of miR-101 were significantly decreased in ICC tissue, as compared with matched adjacent normal tissue. Furthermore, miR-101 was downregulated in the ICC-9810 human ICC cell line, as compared with in the normal human intrahepatic biliary epithelial cell (HIBEC) line. Vascular endothelial growth factor (VEGF)-C was identified as a target gene of miR-101 in ICC-9810 cells. The expression of VEGF-C was negatively regulated by miR-101 at the post-transcriptional level in ICC-9810 cells. Further investigation demonstrated that overexpression of miR-101 markedly suppressed the migration and invasion of ICC-9810 cells, and these effects were similar to those observed following VEGF-C knockdown. Conversely, restoration of VEGF-C reversed the inhibitory effects of miR-101 overexpression on ICC-9810 cell migration and invasion, thus suggesting that miR-101 may suppress ICC-9810 cell migration and invasion, at least partly via inhibition of VEGF-C. It was also demonstrated that the mRNA and protein expression levels of VEGF-C were frequently upregulated in ICC tissue and cells, and its expression level was inversely correlated with that of miR-101 in ICC tissue. In conclusion, the present study identified important roles for miR-101 and VEGF-C in ICC, suggesting that miR-101/VEGF-C signaling may be a promising diagnostic and/or therapeutic target for ICC.