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

Sherry Y. Wu, Rajesha Rupaimoole, Fangrong Shen, Sunila Pradeep, Chad V. Pecot, Cristina Ivan, Archana S. Nagaraja, Kshipra M. Gharpure, Elizabeth Pham, Hiroto Hatakeyama, Michael H. McGuire, Monika Haemmerle, Viviana Vidal-Anaya, Courtney Olsen, Cristian Rodriguez-Aguayo, Justyna Filant, Ehsan A. Ehsanipour, Shelley M. Herbrich, Sourindra N. Maiti, Li HuangJi Hoon Kim, Xinna Zhang, Hee Dong Han, Guillermo N. Armaiz-Pena, Elena G. Seviour, Sue Tucker, Min Zhang, Da Yang, Laurence J.N. Cooper, Rouba Ali-Fehmi, Menashe Bar-Eli, Ju Seog Lee, Prahlad T. Ram, Keith A. Baggerly, Gabriel Lopez-Berestein, Mien Chie Hung, Anil K. Sood

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63 Citations (Scopus)

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.

Original languageEnglish
Article number11169
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 2016 Apr 4
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Wu, S. Y., Rupaimoole, R., Shen, F., Pradeep, S., Pecot, C. V., Ivan, C., Nagaraja, A. S., Gharpure, K. M., Pham, E., Hatakeyama, H., McGuire, M. H., Haemmerle, M., Vidal-Anaya, V., Olsen, C., Rodriguez-Aguayo, C., Filant, J., Ehsanipour, E. A., Herbrich, S. M., Maiti, S. N., ... Sood, A. K. (2016). A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer. Nature Communications, 7, [11169]. https://doi.org/10.1038/ncomms11169