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.
Nature communications. 2016 Apr 04*** epublish ***
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 Huang, Ji 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
Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA., Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA., Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Pathology, Wayne State University School of Medicine, Karmanos Cancer Institute, Detroit, Michigan 48201, USA., Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Medicine, The University of North Carolina, Chapel Hill, North Carolina 27599 USA., Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.