title: Microvesicle-delivery miR-150 promotes tumorigenesis by up-regulating VEGF, and the neutralization of miR-150 attenuate tumor development.
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.
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Liu
authors.forename: Luming
authors.initials: L
authors.lastname: Zhao
authors.forename: Dameng
authors.initials: D
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yin
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yujing
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D055354:Exosomes; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D016372:RNA, Antisense / Q000008:administration & dosage* / Q000235:genetics; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D016372:RNA, Antisense; D042461:Vascular Endothelial Growth Factor A; C533097:MIR150, human