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

被引:116
作者
Liu, Yuchen [1 ]
Zhao, Luming [1 ]
Li, Dameng [1 ]
Yin, Yuan [2 ]
Zhang, Chen-Yu [1 ]
Li, Jing [1 ]
Zhang, Yujing [1 ]
机构
[1] Nanjing Univ, Jiangsu Engn Res Ctr MicroRNA Biol & Biotechnol, State Key Lab Pharmaceut Biotechnol, Sch Life Sci, Nanjing 210093, Jiangsu, Peoples R China
[2] Suzhou Univ, Inst Oncol, Affiliated Hosp 4, Wuxi 214062, Peoples R China
基金
高等学校博士学科点专项科研基金; 中国国家自然科学基金;
关键词
microvesicle; miR-150; tumorigenesis; VEGF; neutralization; attenuation; ENDOTHELIAL GROWTH-FACTOR; MYELOID CELLS; ANGIOGENESIS; MACROPHAGES; MICRORNAS; CANCER; PROGRESSION; MECHANISM; SIRNA;
D O I
10.1007/s13238-013-3092-z
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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.
引用
收藏
页码:932 / 941
页数:10
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