Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer

Oncogene. 2014 Feb 6;33(6):679-89. doi: 10.1038/onc.2012.636. Epub 2013 Jan 28.

Abstract

MicroRNA-155 (miR-155) is frequently upregulated in various types of human cancer; however, its role in cancer angiogenesis remains unknown. Here, we demonstrate the role of miR-155 in angiogenesis through targeting von Hippel-Lindau (VHL) tumour suppressor in breast cancer. Ectopic expression of miR-155 induced whereas knockdown of miR-155 inhibited human umbilical vein endothelial cell network formation, proliferation, invasion and migration. Furthermore, mammary fat pad xenotransplantation of ectopically expressed miR-155 resulted in extensive angiogenesis, proliferation, tumour necrosis and recruitment of pro-inflammatory cells such as tumour-associated macrophages. Expression of VHL abrogated these miR-155 effects. Moreover, miR-155 expression inversely correlates with VHL expression level and is associated with late-stage, lymph node metastasis and poor prognosis, as well as triple-negative tumour in breast cancer. These findings indicate that miR-155 has a pivotal role in tumour angiogenesis by downregulation of VHL, and provide a basis for miR-155-expressing tumours to embody an aggressive malignant phenotype, and therefore miR-155 is an important therapeutic target in breast cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Heterografts
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Prognosis
  • Triple Negative Breast Neoplasms / blood supply*
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology
  • Up-Regulation
  • Von Hippel-Lindau Tumor Suppressor Protein / biosynthesis
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics*
  • Von Hippel-Lindau Tumor Suppressor Protein / metabolism

Substances

  • MIRN155 microRNA, human
  • MicroRNAs
  • Von Hippel-Lindau Tumor Suppressor Protein
  • VHL protein, human