Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms11169
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Funding
- Ovarian Cancer Research Fund Alliance
- Foundation for Women's Cancer
- Texas Center for Cancer Nanomedicine
- Cancer Prevention Research Institute of Texas [RP101502, RP101489]
- Russell and Diana Hawkins Family Foundation
- Jiangsu Health International Exchange Program Fellowship
- NCI [CA009666]
- Canadian Institutes of Health Research
- Ovarian Cancer Canada
- Deutsche Forschungsgemeinschaft Research Fellowship
- Immatics US
- NIH [GM100777-01, GM086937-01, GM084552-04, CA016672, CA109298, P50 CA083639, P50 CA098258, CA128797, U54 CA151668, UH2 TR000943, U24CA143835, P30CA16672]
- NCI-DHHS-NIH [T32 CA101642]
- DOD [OC120547, 00093416]
- Ovarian Cancer Research Fund, Inc.
- Blanton-Davis Ovarian Cancer Research Program
- RGK Foundation
- Gilder Foundation
- Betty Anne Asche Murray Distinguished Professorship
- Cancer Center Support Grant [NCI CA016672]
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A deeper mechanistic understanding of tumour angiogenesis regulation is needed to improve current anti-angiogenic therapies. Here we present evidence from systems-based miRNA analyses of large-scale patient data sets along with in vitro and in vivo experiments that miR-192 is a key regulator of angiogenesis. The potent anti-angiogenic effect of miR-192 stems from its ability to globally downregulate angiogenic pathways in cancer cells through regulation of EGR1 and HOXB9. Low miR-192 expression in human tumours is predictive of poor clinical outcome in several cancer types. Using 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) nanoliposomes, we show that miR-192 delivery leads to inhibition of tumour angiogenesis in multiple ovarian and renal tumour models, resulting in tumour regression and growth inhibition. This anti-angiogenic and anti-tumour effect is more robust than that observed with an anti-VEGF antibody. Collectively, these data identify miR-192 as a central node in tumour angiogenesis and support the use of miR-192 in an anti-angiogenesis therapy.
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