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Copyright Nature Publishing Group Apr 2016

Abstract

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.

Details

Title
A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer
Author
Wu, Sherry Y; Rupaimoole, Rajesha; Shen, Fangrong; Pradeep, Sunila; Pecot, Chad V; Ivan, Cristina; Nagaraja, Archana S; Gharpure, Kshipra M; Pham, Elizabeth; Hatakeyama, Hiroto; Mcguire, Michael H; Haemmerle, Monika; Vidal-anaya, Viviana; Olsen, Courtney; Rodriguez-aguayo, Cristian; Filant, Justyna; Ehsanipour, Ehsan A; Herbrich, Shelley M; Maiti, Sourindra N; Huang, Li; Kim, Ji Hoon; Zhang, Xinna; Han, Hee-dong; Armaiz-pena, Guillermo N; Seviour, Elena G; Tucker, Sue; Zhang, Min; Yang, Da; Cooper, Laurence J N; Ali-fehmi, Rouba; Bar-eli, Menashe; Lee, Ju-seog; Ram, Prahlad T; Baggerly, Keith A; Lopez-berestein, Gabriel; Hung, Mien-chie; Sood, Anil K
Pages
11169
Publication year
2016
Publication date
Apr 2016
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1778075753
Copyright
Copyright Nature Publishing Group Apr 2016