MicroRNA-9 suppresses uveal melanoma cell migration and invasion through the NF-κB1 pathway

Oncol Rep. 2012 Sep;28(3):961-8. doi: 10.3892/or.2012.1905. Epub 2012 Jul 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Melanoma / pathology*
  • MicroRNAs / physiology*
  • NF-kappa B p50 Subunit / genetics
  • NF-kappa B p50 Subunit / metabolism*
  • Neoplasm Invasiveness
  • RNA Interference
  • Signal Transduction
  • Uveal Neoplasms / pathology*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • MIRN92 microRNA, human
  • MicroRNAs
  • NF-kappa B p50 Subunit
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9

Supplementary concepts

  • Uveal melanoma