Colorectal cancer cell-derived microvesicles containing microRNA-1246 promote angiogenesis by activating Smad 1/5/8 signaling elicited by PML down-regulation in endothelial cells

Biochim Biophys Acta. 2014 Nov;1839(11):1256-72. doi: 10.1016/j.bbagrm.2014.09.002. Epub 2014 Sep 10.


Emerging studies on circulating microRNAs (miRNAs) or microvesicles (MVs) have shown the potential of them to be novel biomarkers and therapeutic targets for cancer. However, the biological roles of these miRNAs and MVs have not been validated yet. To determine the biological significance of MVs, we used human colorectal cancer cells as the MV donor and endothelial cells (HUVECs) as the MV recipient and demonstrated the transfer of colorectal cancer cell-derived MVs (CRC-MVs) to HUVECs and evaluated the roles of these MVs and their cargo in tumor angiogenesis. Consequently, the incubation of HUVECs with CRC-MVs promoted the proliferation, migration, and tube formation activities of these cells. Among the cargoes shuttled by the MVs, miR-1246 and TGF-β were considered to be responsible for the pro-angiogenic function of MVs by activating Smad 1/5/8 signaling in the HUVECs. These results suggest that colorectal cancer cells secreted MVs to contribute to tumor angiogenesis.

Keywords: Angiogenesis; Colorectal cancer; Microvesicles; Smad signaling; miR-1246.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Colorectal Neoplasms / blood supply
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Cytoplasmic Vesicles / pathology*
  • Cytoplasmic Vesicles / physiology
  • Down-Regulation / genetics
  • Endothelial Cells / metabolism*
  • HeLa Cells
  • Hep G2 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / pathology
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Promyelocytic Leukemia Protein
  • Signal Transduction / genetics
  • Smad1 Protein / genetics
  • Smad1 Protein / metabolism
  • Smad5 Protein / genetics
  • Smad5 Protein / metabolism
  • Smad8 Protein / genetics
  • Smad8 Protein / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism


  • MIRN1246 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • SMAD1 protein, human
  • SMAD5 protein, human
  • SMAD9 protein, human
  • Smad1 Protein
  • Smad5 Protein
  • Smad8 Protein
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human