Abstract
MicroRNA-431 (miR-431) has been recognized as an oncogenic miRNA, being implicated in the initiation and development of human cancers. Recently, deregulation of miR-431 has been reported in several tumors. However, the clinical significance of miR-431 and its underlying role in human hepatocellular carcinoma (HCC) are poorly explored. Herein, we found that miR-431 expression was reduced in HCC tissues compared to noncancerous tissues. Otherwise, down-regulation of miR-431 was observed in aggressive tumor tissues. The levels of miR-431 expression in HCC cell lines were significantly lower than that in a nontransformed hepatic cell line. Clinical association analyses disclosed that a low level of miR-431 was prominently associated with poor prognostic features of HCC including venous infiltration, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) tumor stage. Our in vitro studies showed that up-regulation of miR-431 expression reduced cell invasion and migration in HCCLM3 cells. In contrast, down-regulation of miR-431 expression promoted SMMC-7721 cell invasion and migration. We found that up-regulation of miR-431 expression decreased zinc finger E-box binding homeobox 1 (ZEB1) expression and inhibited the epithelial-mesenchymal transition (EMT) with increased E-cadherin expression and decreased vimentin expression in HCCLM3 cells. Otherwise, down-regulation of miR-431 expression increased ZEB1 expression and promoted EMT in SMMC-7721 cells. Significantly, ZEB1 was identified as a target of miR-431 in HCC. ZEB1 knockdown abrogated the effect of miR-431 silencing on EMT and cell mobility in SMMC-7721 cells. In conclusion, miR-431 inhibits migration and invasion of HCC cells by suppressing ZEB1-mediated EMT.