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Microvesicle-delivery miR-150 promotes tumorigenesis by up-regulating VEGF, and the neutralization of miR-150 attenuate tumor development |
Yuchen Liu1, Luming Zhao1, Dameng Li1, Yuan Yin2, Chen-Yu Zhang1(), Jing Li1(), Yujing Zhang1() |
1. Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China; 2. Oncology Institute, Fourth Affiliated Hospital of Suzhou University, Wuxi 214062, China |
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Abstract 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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Keywords
microvesicle
miR-150
tumorigenesis
VEGF
neutralization
attenuation
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Corresponding Author(s):
Zhang Chen-Yu,Email:cyzhang@nju.edu.cn; Li Jing,Email:jingli220@nju.edu.cn; Zhang Yujing,Email:yjzhang@nju.edu.cn
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Issue Date: 01 December 2013
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