MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells

Prue N. Plummer, Ruth Freeman, Ryan J. Taft, Jelena Vider, Michael Sax, Brittany A. Umer, Dingcheng Gao, Christopher Johns, John S. Mattick, Stephen D. Wilton, Vito Ferro, Nigel A.J. McMillan, Alexander Swarbrick, Vivek Mittal, Albert S. Mellick

Research output: Contribution to journalArticlepeer-review

123 Scopus citations


Bone marrow-derived endothelial progenitor cells (EPC) contribute to the angiogenesis-dependent growth of tumors in mice and humans. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors and by direct luminal incorporation into sprouting nascent vessels. miRNAs have emerged as key regulators of several cellular processes including angiogenesis; however, whether miRNAs contribute to bone marrow-mediated angiogenesis has remained unknown. Here, we show that genetic ablation of miRNA-processing enzyme Dicer, specifically in the bone marrow, decreased the number of circulating EPCs, resulting in angiogenesis suppression and impaired tumor growth. Furthermore, genome-wide deep sequencing of small RNAs revealed tumor EPC-intrinsic miRNAs including miR-10b and miR-196b, which have been previously identified as key regulators of HOX signaling and adult stem cell differentiation. Notably, we found that both miR-10b and miR-196b are responsive to vascular endothelial growth factor stimulation and show elevated expression in human high-grade breast tumor vasculature. Strikingly, targeting miR-10b and miR-196b led to significant defects in angiogenesis-mediated tumor growth in mice. Targeting these miRNAs may constitute a novel strategy for inhibiting tumor angiogenesis.

Original languageEnglish (US)
Pages (from-to)341-352
Number of pages12
JournalCancer research
Issue number1
StatePublished - Jan 1 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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