[Show abstract][Hide abstract] ABSTRACT: The aggressive course of uveal melanoma is believed to reflect its unusually invasive and metastatic nature, which is associated with the nuclear factor kappaB (NF-κB) pathway. MicroRNAs (miRNAs) have been implicated in the regulation of various biological and pathological processes in cancer, however, the special role of miR-9 in uveal melanoma metastasis is largely unknown. In the present study, we showed that miR-9 is significantly reduced in highly invasive uveal melanoma cell lines, and suppressed migration and invasion of highly invasive cells. Furthermore, miR-9 negatively modulated NF-κB1 expression by direct targeting at its 3'-UTRs. Additionally, downstream targets of NF-κB1, such as MMP-2, MMP-9 and VEGFA, were regulated by miR-9 in the same pattern as NF-κB1. Therefore, miR-9 suppresses uveal melanoma cell migration and invasion partly through downregulation of the NF-κB1 signaling pathway.
[Show abstract][Hide abstract] ABSTRACT: Genistein, an isoflavone isolated from soybean, has been found to be a potent antitumor agent. However, both the effect of genistein on human uveal melanoma cells and the precise mechanism by which genistein suppresses tumorigenesis remain unclear. In the present study, we explored the possible activity of genistein to inhibit human uveal melanoma cell growth and investigated the possible role of genistein on microRNA-27a (miR-27a) as well as its target gene zinc finger and BTB domain containing 10 (ZBTB10) expression levels. The results suggested a significant inhibition of uveal melanoma cell growth in a time- and dose-related manner. In vivo study also indicated treatment groups with genistein could significantly inhibit the growth of xenografts. Further functional assays revealed that the levels of miR-27a and its target gene ZBTB10 were significantly different based on the dose of genistein. In conclusion, the present study demonstrates that genistein exerts growth inhibitory activities in human uveal melanoma cells. Moreover, we for the first time report a correlation between antitumor activity of genistein and miR-27a mediated regulatory mechanism.