4.7 Article

Microvesicle-delivery miR-150 promotes tumorigenesis by up-regulating VEGF, and the neutralization of miR-150 attenuate tumor development

Journal

PROTEIN & CELL
Volume 4, Issue 12, Pages 932-941

Publisher

SPRINGEROPEN
DOI: 10.1007/s13238-013-3092-z

Keywords

microvesicle; miR-150; tumorigenesis; VEGF; neutralization; attenuation

Categories

Funding

  1. National Basic Research Program (973 Program) [2014CB542300]
  2. National Natural Science Foundation of China [31200969, 31200874, 81101330, 31271378, 81250044]
  3. National Science Fund for Distinguished Young Scholars [81025019]
  4. Natural Science Foundation of Jiangsu Province [BK2011013, BK2012014]
  5. Research Fund for the Doctoral Program of Higher Education of China [20120091120044]

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Tumor-associated macrophages (TAMs) mostly exhibit M2-like (alternatively activated) properties and play positive roles in angiogenesis and tumorigenesis. Vascular endothelial growth factor (VEGF) is a key angiogenic factor. During tumor development, TAMs secrete VEGF and other factors to promote angiogenesis; thus, anti-treatment against TAMs and VEGF can repress cancer development, which has been demonstrated in clinical trials and on an experimental level. In the present work, we show that miR-150 is an oncomir because of its promotional effect on VEGF. MiR-150 targets TAMs to up-regulate their secretion of VEGF in vitro. With the utilization of cell-derived vesicles, named microvesicles (MVs), we transferred antisense RNA targeted to miR-150 into mice and found that the neutralization of miR-150 down-regulates miR-150 and VEGF levels in vivo and attenuates angiogenesis. Therefore, we proposed the therapeutic potential of neutralizing miR-150 to treat cancer and demonstrated a novel, natural, microvesicle-based method for the transfer of nucleic acids.

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