Hepatocellular carcinoma is one of the most common and lethal cancers worldwide, especially in developing countries. In the present study, we found that the expression of a microRNA, miR-590-5P, was down-regulated and S100A10 was up-regulated in six hepatocellular carcinoma cell lines. The reporter gene assay showed that overexpression of miR-590-5P effectively reduced the activity of luciferase expressed by a vector bearing the 3' untranslated region of S100A10 mRNA. Ectopic miR-590-5P overexpression mediated by lentiviral infection decreased expression of S100A10. Infection of Lv-miR-590-5P inhibited cell growth and induced cell cycle G1 arrest in HepG2 cells. In addition, miR-590-5P expression suppressed the expression of Wnt5a, cMyc and cyclin D1, and increased the phosphorylation of β-catenin and expression of Caspase 3, which may contribute to the inhibitory effect of miR-590-5P on cell growth. Taken together, our data suggest that down-regulation of miR-590-5P is involved in hepatocellular carcinoma and the restoration of miR-590-5P can impair the growth of cancer cells, suggesting that miR-590-5P may be a potential target molecule for the therapy of hepatocellular carcinoma.

The zinc finger protein Snail1 is an important factor in the regulation of the epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells. The present study demonstrated that the expression of Snail1 in HCC tissues was significantly higher compared with its expression in tissues adjacent to primary sites, as determined via western blotting. Furthermore, the results of a dual luciferase assay revealed that hsa-microRNA(miR)199a-5p negatively regulated the protein expression of Snail1 by binding to its 3 ' untranslated region. However, in a comparative analysis of primary HCC and its metastatic tissues using reverse transcription-quantitative polymerase chain reaction and western blotting, it was demonstrated that the expression of hsa-miR199a-5p and Snail1 in HCC metastatic tissues were significantly higher compared with primary lesions and an association between them identified that hsa-miR199a-5p lost its ability to negatively regulate Snail1. This result is contradictive to the fact that hsa-miR199a-5p inhibits the expression of the Snail1 protein. The present study hypothesized that the aberrant expression of long non-coding RNA was the cause of hsa-miR199a-5p inactivation based on loss of function rather than a reduction in content. The data collected in the present study confirmed the hypothesis that AB209371 binds to hsa-miR199a-5p and weakened the inhibitory effect of hsa-miR199a-5p on Snail1 expression. In addition, an in vitro EMT model was established in the present study by inducing HCC cells with TGF-beta 1. The results revealed that AB209371 silencing effectively reversed the hsa-miR199a-5p mediated inhibition of EMT by negatively regulating Snail1 protein expression. Therefore, AB209371 silencing in combination with hsa-miR199a-5p expression may serve as an effective means to inhibit EMT in HCC cells. The present study also revealed that hsa-miR199a-5p/Snail1 exhibits a dominant regulatory effect in the EMT of HCC cells via a Snail1 recovery experiment. In conclusion, to the best of our knowledge, the present study confirmed for the first time that the high expression of AB209371 is favorable for the EMT in HCC cells and may be a direct cause of hsa-miR199a-5p inactivation (an HCC metastasis suppressor). Additionally, AB209371 silencing combined with hsa-miR199a-5p overexpression may be an effective means to inhibit the metastasis of HCC and the EMT of HCC cells.