Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province, PR China.
Oncol Rep. 2012 Sep;28(3):961-8. doi: 10.3892/or.2012.1905. Epub 2012 Jul 6.
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.
葡萄膜黑色素瘤的侵袭性进程被认为反映了其异常的侵袭和转移特性，这与核因子 kappaB（NF-κB）通路有关。MicroRNAs（miRNAs）已被牵涉到癌症中各种生物学和病理学过程的调控中，然而，miR-9 在葡萄膜黑色素瘤转移中的特殊作用在很大程度上仍是未知的。在本研究中，我们表明 miR-9 在高度侵袭性的葡萄膜黑色素瘤细胞系中显著减少，并抑制了高度侵袭性细胞的迁移和侵袭。此外，miR-9 通过直接靶向其 3'-UTRs 负调控 NF-κB1 的表达。此外，NF-κB1 的下游靶标，如 MMP-2、MMP-9 和 VEGFA，也以与 NF-κB1 相同的方式受 miR-9 的调控。因此，miR-9 通过下调 NF-κB1 信号通路抑制葡萄膜黑色素瘤细胞的迁移和侵袭。
