A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer

Sherry Y. Wu(The University of Texas MD Anderson Cancer Center), Rajesha Rupaimoole(The University of Texas MD Anderson Cancer Center), Fangrong Shen(The University of Texas MD Anderson Cancer Center), Sunila Pradeep(The University of Texas MD Anderson Cancer Center), Chad V. Pecot(University of North Carolina at Chapel Hill), Cristina Ivan(The University of Texas MD Anderson Cancer Center), Archana S. Nagaraja(The University of Texas MD Anderson Cancer Center), Kshipra M. Gharpure(The University of Texas MD Anderson Cancer Center), Elizabeth Pham(Sunnybrook Health Science Centre), Hiroto Hatakeyama(The University of Texas MD Anderson Cancer Center), Michael H. McGuire(The University of Texas MD Anderson Cancer Center), Monika Haemmerle(The University of Texas MD Anderson Cancer Center), Viviana Vidal‐Anaya(The University of Texas MD Anderson Cancer Center), Courtney Olsen(The University of Texas MD Anderson Cancer Center), Cristian Rodriguez‐Aguayo(The University of Texas MD Anderson Cancer Center), Justyna Filant(The University of Texas MD Anderson Cancer Center), Ehsan A. Ehsanipour(The University of Texas MD Anderson Cancer Center), Shelley M. Herbrich(The University of Texas MD Anderson Cancer Center), Sourindra N. Maiti(The University of Texas MD Anderson Cancer Center), Li Huang(The University of Texas MD Anderson Cancer Center), Ji Hoon Kim(The University of Texas MD Anderson Cancer Center), Xinna Zhang(The University of Texas MD Anderson Cancer Center), Hee‐Dong Han(The University of Texas MD Anderson Cancer Center), Guillermo N. Armaiz-Peña(The University of Texas MD Anderson Cancer Center), Elena G. Seviour(The University of Texas MD Anderson Cancer Center), Sue Tucker(The University of Texas MD Anderson Cancer Center), Min Zhang(University of Pittsburgh), Da Yang(University of Pittsburgh), Laurence J.N. Cooper(The University of Texas MD Anderson Cancer Center), Rouba Ali‐Fehmi(Wayne State University), Menashe Bar‐Eli(The University of Texas MD Anderson Cancer Center), Ju‐Seog Lee(The University of Texas MD Anderson Cancer Center), Prahlad T. Ram(The University of Texas MD Anderson Cancer Center), Keith Baggerly(The University of Texas MD Anderson Cancer Center), Gabriel Lopez‐Berestein(University of North Carolina at Chapel Hill), Mien‐Chie Hung(The University of Texas MD Anderson Cancer Center), Anil K. Sood(The University of Texas MD Anderson Cancer Center)
Nature Communications
April 4, 2016
10.1038/ncomms11169
Cited by 119Open Access
Full Text

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.

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