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Background  Micro-ribonucleic acid (miRNA)-199a-5p has been reported to be decreased in hepatocellular carcinoma (HCC) compared to normal tissue. Discoidin domain receptor-1 (DDR1) tyrosine kinase, involved in cell invasion-related signaling pathway, was predicted to be a potential target of miR-199a-5p by the use of miRNA target prediction algorithms. The aim of this study was to investigate the role of miR-199a-5p and DDR1 in HCC invasion.    Methods  Mature miR-199a-5p and  DDR1  expression were evaluated in tumor and adjacent non-tumor liver tissues from 23 patients with HCC undergoing liver resection and five hepatoma cell lines by the use of real-time quantitative RT-PCR (qRT-PCR) analysis. The effect of aberrant miR-199a-5p expression on cell invasion was assessed  in vitro  using HepG2 and SNU-182 hepatoma cell lines. Luciferase reporter assay was employed to validate  DDR1  as a putative miR-199a-5p target gene. Regulation of  DDR1  expression by miR-199a-5p was assessed by the use qRT-PCR and western blotting analysis.    Results  A significant down-regulation of miR-199a-5p was observed in 65.2% of HCC tissues and in four of five cell lines. In contrast,  DDR1  expression was significantly increased in 52.2% of HCC samples and in two of five cell lines. Increased  DDR1  expression in HCC was associated with advanced tumor stage.  DDR1  was shown to be a direct target of miR-199a-5p by luciferase reporter assay. Transfection of miR-199a-5p inhibited invasion of HepG2 but not SNU-182 hepatoma cells.    Conclusions  Decreased expression of miR-199a-5p contributes to increased cell invasion by functional deregulation of  DDR1  activity in HCC. However, the effect of miR-199a-5p on  DDR1  varies among individuals and hepatoma cell lines. These findings may have significant translational relevance for development of new targeted therapies as well as prognostic prediction for patients with HCC.

Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion