Therapeutic Delivery of mIRNAs to Inhibit Tumor Angiogenesis

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October 25, 2013

Tumor angiogenesis, formation of neovasculature from pre-existing blood vessels, allows tumor cells to grow and facilitates metastasis. Therefore, inhibition of tumor angiogenesis has emerged as an attractive therapy, with a number of drugs currently in the clinic. Here, we identified novel anti-angiogenic miRNA by using a lentiviral miRNA expression library of 1120 human miRNAs. The anti-angiogenic properties of the identified miRNAs were determined by using several in vitro angiogenesis assays. The most robust anti-angiogenic miRNA (miR-7) has not been associated with angiogenesis inhibition before. Local or systemic delivery of miR-7 in a murine tumor models reduced growth rate by ~50%, and also inhibited the tumor vascularization. An RNA-seq experiment revealed that 1100 genes were significantly up and down regulated. In this study we not only show the identification of novel anti-angiogenic miRNA, but also their activity in in vitro and in vivo models. We identified novel target genes affected by this miRNA. The characterization of this miRNA demonstrates its therapeutic value to treat tumor angiogenesis and to identify new pathways involved in tumor neovascularization.

Drug DiscoveryGenomicsInformatics

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