Exosome-Derived miR-130a Activates Angiogenesis in Gastric Cancer by Targeting C-MYB in Vascular Endothelial Cells

Mol Ther. 2018 Oct 3;26(10):2466-2475. doi: 10.1016/j.ymthe.2018.07.023. Epub 2018 Aug 4.

Abstract

Metastasis is a crucial reason for the poor prognosis of gastric cancer. Angiogenesis is closely associated with tumor invasion and metastasis. Cancer-derived exosomes play an important role in the establishment of the tumor microenvironment. In this study, exosomes were isolated by sequential differential centrifugation, and they were verified by transmission electron microscopy. Changes in the biological behavior of human umbilical vein endothelial cells were evaluated with downstream cellular functional experiments. The RNA and protein levels of the miRNA target gene were determined by real-time qPCR and western blotting. A mouse xenograft model was adopted to evaluate the correlation between exosome-derived miR-130a and tumor growth in vivo. We demonstrated that exosomes delivered miR-130a from gastric cancer cells into vascular cells to promote angiogenesis and tumor growth by targeting c-MYB both in vivo and in vitro. miR-130a packaged in exosomes secreted from cancer cells acts as a driver of angiogenesis. Therefore, miR-130a might be a potential biomarker for monitoring the activity of gastric cancer. In addition, suppressing the expression or blocking the transmission of these exosomes might be a novel antiangiogenic therapeutic strategy for gastric cancer.

Keywords: antiangiogenesis; c-MYB; exosomes; gastric cancer; invasion; metastasis; miR-130a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Endothelial Cells / pathology
  • Exosomes / genetics
  • Gene Expression Regulation, Neoplastic
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / pathology
  • Proto-Oncogene Proteins c-myb / antagonists & inhibitors
  • Proto-Oncogene Proteins c-myb / genetics*
  • Signal Transduction / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • MIRN130 microRNA, human
  • MYB protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myb