Faculty Collaboration Database

A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer. Nat Commun 2016 Apr 04;7:11169

Date

04/05/2016

Pubmed ID

27041221

Pubmed Central ID

PMC4822037

DOI

10.1038/ncomms11169

Scopus ID

2-s2.0-84962728482 (requires institutional sign-in at Scopus site)   118 Citations

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.

Author List

Wu SY, Rupaimoole R, Shen F, Pradeep S, Pecot CV, Ivan C, Nagaraja AS, Gharpure KM, Pham E, Hatakeyama H, McGuire MH, Haemmerle M, Vidal-Anaya V, Olsen C, Rodriguez-Aguayo C, Filant J, Ehsanipour EA, Herbrich SM, Maiti SN, Huang L, Kim JH, Zhang X, Han HD, Armaiz-Pena GN, Seviour EG, Tucker S, Zhang M, Yang D, Cooper LJ, Ali-Fehmi R, Bar-Eli M, Lee JS, Ram PT, Baggerly KA, Lopez-Berestein G, Hung MC, Sood AK

Author

Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Line, Tumor
Down-Regulation
Early Growth Response Protein 1
Female
Gene Regulatory Networks
Genetic Therapy
Homeodomain Proteins
Humans
Kidney Neoplasms
Mice
MicroRNAs
Neovascularization, Pathologic
Ovarian Neoplasms
Phosphatidylcholines
Tumor Burden