microRNA-141 inhibits cell proliferation and invasion and promotes apoptosis by targeting hepatocyte nuclear factor-3β in hepatocellular carcinoma cells

Background: Hepatocyte nuclear factor-3 beta (HNF-3 beta) plays a critical role in hepatocyte differentiation and controls liver-specific gene expression during the development of hepatocellular carcinoma (HCC), but the molecular basis of this process has not been fully elucidated. microRNAs (miRNAs) are powerful, post-transcriptional regulators of gene expression. Whether miRNAs can impact the effects of HNF-3 beta in HCC is still unknown. Methods: HNF-3 beta and miR-141 expression levels were detected in HepG2 cells, using real-time quantitative RT PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate HNF-3 beta as a direct target gene of miR-141. Cell proliferation, invasion, and apoptosis were also examined to confirm whether miR-141 could impact on HNF-3 beta in HCC. Results: In this study, we found that HNF-3 beta protein levels were consistently upregulated in HCC clinical tissues compared with matched normal adjacent tissues. However, the mRNA levels of HNF-3 beta varied in random tissues, suggesting that a post-transcriptional mechanism was involved in its regulation. We used bioinformatic analyses to search for miRNAs that could potentially target HNF-3 beta, and identified specific targeting sites for miR-141 in the 3'-untranslated region (3'-UTR) of the HNF-3 beta gene. By overexpressing miR-141 in HepG2 cells, we experimentally validated that miR-141 directly regulated HNF-3 beta expression. Furthermore, the biological consequences of targeting HNF-3 beta by miR-141 were examined using cell proliferation, invasion and apoptosis assays in vitro. We demonstrated that the repression of HNF-3 beta by miR-141 suppressed the proliferation and invasion and promoted the apoptosis of HepG2 cells. Conclusions: miR-141 functions as a tumor suppressor in HCC cells through the inhibition of HNF-3 beta translation.