Cancer-derived Circulating MicroRNAs Promote Tumor Angiogenesis by Entering Dendritic Cells to Degrade Highly Complementary MicroRNAs

Theranostics. 2017 Mar 24;7(6):1407-1421. doi: 10.7150/thno.18262. eCollection 2017.

Abstract

Understanding the interaction between cancer cells and immunocytes will inspire new cancer therapy strategies. However, how cancer-derived circulating miRNAs modulate such interaction remains unclear. Here we discovered that circulating miR-410-5p, secreted by prostate cancer cells, entered dendritic cells (DCs), with the aid of argonaute-2 protein. The cancer cell antigens stimulated the DCs to produce miR-410-3p, a highly complementary counterpart of miR-410-5p derived from pre-miR-410. The DC-internalized miR-410-5p degraded the miR-410-3p by base pairing and thus inhibited its function in suppressing tumor angiogenesis, promoting tumor growth. Furthermore, blockade of the miR-410-5p upregulated the miR-410-3p to inhibit tumor growth. Our work suggests a new miRNA-mediated role of immunocytes in cancer progression and a new strategy of cancer therapy through suppressing circulating miRNAs.

Keywords: cancer angiogenesis; circulating microRNA; dendritic cells; prostate cancer..

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Circulating MicroRNA / metabolism*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Humans
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Neovascularization, Pathologic / physiopathology*
  • Prostatic Neoplasms / pathology*
  • RNA Stability*

Substances

  • Circulating MicroRNA
  • MIRN410 microRNA, human
  • MIRN423 microRNA, human
  • MicroRNAs
  • Mirn423 microRNA, mouse