Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma
Babae, Negar; Bourajjaj, Meriem; Liu, Yijia; Van Beijnum, Judy R.; Cerisoli, Francesco; Scaria, Puthupparampil V.; Verheul, Mark; Van Berkel, Maaike P.; Pieters, Ebel H E; Van Haastert, Rick J.; Yousefi, Afrouz; Mastrobattista, Enrico; Storm, Gert; Berezikov, Eugene; Cuppen, Edwin; Woodle, Martin; Schaapveld, Roel Q J; Prevost, Gregoire P.; Griffioen, Arjan W.; Van Noort, Paula I.; Schiffelers, Raymond M.
(2014) Oncotarget, volume 5, issue 16, pp. 6687 - 6700
(Article)
Abstract
Tumor-angiogenesis is the multi-factorial process of sprouting of endothelial cells (EC) into micro-vessels to provide tumor cells with nutrients and oxygen. To explore miRNAs as therapeutic angiogenesis-inhibitors, we performed a functional screen to identify miRNAs that are able to decrease EC viability. We identified miRNA-7 (miR-7) as a potent negative
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regulator of angiogenesis. Introduction of miR-7 in EC resulted in strongly reduced cell viability, tube formation, sprouting and migration. Application of miR-7 in the chick chorioallantoic membrane assay led to a profound reduction of vascularization, similar to anti-angiogenic drug sunitinib. Local administration of miR-7 in an in vivo murine neuroblastoma tumor model significantly inhibited angiogenesis and tumor growth. Finally, systemic administration of miR-7 using a novel integrin-targeted biodegradable polymeric nanoparticles that targets both EC and tumor cells, strongly reduced angiogenesis and tumor proliferation in mice with human glioblastoma xenografts. Transcriptome analysis of miR-7 transfected EC in combination with in silico target prediction resulted in the identification of OGT as novel target gene of miR-7. Our study provides a comprehensive validation of miR-7 as novel anti-angiogenic therapeutic miRNA that can be systemically delivered to both EC and tumor cells and offers promise for miR-7 as novel anti-tumor therapeutic.
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Keywords: Angiogenesis, Delivery, MicroRNA, miR-7, Therapy, Oncology, General Medicine, Journal Article, Research Support, Non-U.S. Gov't
ISSN: 1949-2553
Publisher: Impact Journals
(Peer reviewed)