microRNA-216b inhibits cell proliferation and migration in human melanoma by targeting FOXM1 in vitro and in vivo

Cell Biol Int. 2017 Dec;41(12):1272-1282. doi: 10.1002/cbin.10754. Epub 2017 Sep 10.

Abstract

MicroRNAs (miRNAs) play an increasingly important role in cancer growth by coordinately suppressing genes that control cell migration, proliferation, and invasion. The above results can be achieved through the regulation of gene expression by miRNAs by suppressing translation or the direct sequence-specific degradation of the targeted mRNA. In the present study, we indicate that the expression of miR-216b could be effectively repressed both in human melanoma tissues through a comparison with primary melanoma and in human melanoma cell lines through a comparison with a normal human keratinocyte line. Moreover, miR-216b induced a clear decrease in melanoma cell proliferation and migration in vitro. Forkhead box M1 (FOXM1) was confirmed as a target gene of miR-216b, and the overexpression of miR-216b markedly repressed the luciferase activity of reporter plasmids containing the FOXM1 3'-UTR (untranslated region). Furthermore, miR-216b suppressed melanoma cell growth in nude mice in vivo, with the effects of miR-216b overexpression on melanoma cell growth and proliferation reversed by FOXM1 overexpression. The results demonstrated that miR-216b is a tumor suppressor in melanoma, identified the FOXM1 signaling pathway as a target of miR-216b action, and suggested a potential therapeutic role for miR-216b in melanoma.

Keywords: FOXM1; melanoma; miR-216b.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Forkhead Box Protein M1 / genetics*
  • Forkhead Box Protein M1 / metabolism*
  • Genes, Tumor Suppressor
  • HEK293 Cells
  • Heterografts
  • Humans
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Mice
  • Mice, Inbred NOD
  • Mice, Nude
  • Mice, SCID
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction

Substances

  • 3' Untranslated Regions
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • MIRN216 microRNA, human
  • MicroRNAs
  • RNA, Messenger