Microvesicle-delivery miR-150 promotes tumorigenesis by up-regulating VEGF, and the neutralization of miR-150 attenuate tumor development.
10.1007/s13238-013-3092-z
- Author:
Yuchen LIU
1
;
Luming ZHAO
;
Dameng LI
;
Yuan YIN
;
Chen-Yu ZHANG
;
Jing LI
;
Yujing ZHANG
Author Information
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.
- Publication Type:Journal Article
- MeSH:
Animals;
Carcinogenesis;
genetics;
metabolism;
pathology;
Cell Line, Tumor;
Exosomes;
HEK293 Cells;
Heterografts;
Humans;
Macrophages;
metabolism;
Male;
Mice;
Mice, Inbred C57BL;
MicroRNAs;
genetics;
metabolism;
Neoplasm Transplantation;
RNA, Antisense;
administration & dosage;
genetics;
Up-Regulation;
Vascular Endothelial Growth Factor A;
genetics;
metabolism
- From:
Protein & Cell
2013;4(12):932-941
- CountryChina
- Language:English
-
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.
