MicroRNA-125b suppresses the epithelial-mesenchymal transition and cell invasion by targeting ITGA9 in melanoma

Tumour Biol. 2016 May;37(5):5941-9. doi: 10.1007/s13277-015-4409-8. Epub 2015 Nov 23.

Abstract

Increasing evidence has shown that aberrant miRNAs contribute to the development and progression of human melanoma. Previous studies have shown that miR-125b functions as a suppressor in malignant melanoma. However, the molecular function and mechanism by which miR-125b influences melanoma growth and invasion are still unclear. In this study, we aimed to investigate the role of miR-125b in melanoma progression and metastasis. We found that miR-125b expression is significantly downregulated in primary melanoma, and an even greater downregulation was observed in metastatic invasion. Restored expression of miR-125b in melanoma suppressed cell proliferation and invasion both in vitro and in vivo. Furthermore, our findings demonstrate that upregulating miR-125b significantly inhibits malignant phenotypes by repressing the expression of integrin alpha9 (ITGA9). Finally, our data reveal that upregulated expression of ITGA9 in melanoma tissues is inversely associated with miR-125b levels. Together, our results demonstrate that upregulation of ITGA9 in response to the decrease in miR-125b in metastatic melanoma is responsible for melanoma tumor cell migration and invasion.

Keywords: EMT; ITGA9; Invasion; Melanoma; miR-125b.

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Adhesion / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrins / chemistry
  • Integrins / genetics*
  • Melanoma / genetics*
  • Melanoma / pathology*
  • Mice
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • Neoplasm Metastasis
  • RNA Interference*
  • Xenograft Model Antitumor Assays

Substances

  • ITGA9 protein, human
  • Integrins
  • MIRN125 microRNA, human
  • MicroRNAs