摘要
Tumor-associated macrophages(TAMs)mostly exhibit M2-like(alternatively activated)properties and play posi-tive roles in angiogenesis and tumorigenesis.Vascular en-dothelial 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 secre-tion of VEGF in vitro.With the utilization of cell-derived vesicles,named microvesicles(MVs),we transferred an-tisense 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.There-fore,we proposed the therapeutic potential of neutralizing miR-150 to treat cancer and demonstrated a novel,natu-ral,microvesicle-based method for the transfer of nucleic acids.
基金
This work was supported by grants from the National Basic Research Program(973 Program)(No.2014CB542300)
the National Natural Science Foundation of China(Grant Nos.31200969,31200874,81101330,31271378,and 81250044)
the National Science Fund for Distinguished Young Scholars(81025019)
the Natural Science Foun-dation of Jiangsu Province(BK2011013 and BK2012014)
the Research Fund for the Doctoral Program of Higher Education of China(20120091120044).