ROLE OF MIRNA-451 IN THE HYPOXIA-INDUCED PRO-ANGIOGENIC RESPONSE OF GLIOBLASTOMA
Led by David Zagzag, MD, PhD at New York University
Given the well-established role of hypoxia in glioma angiogenesis, targeting a hypoxia-induced mechanism implicated in angiogenesis is critical for developing a successful treatment for glioblastoma (GBM). Recently, microRNAs (miRNAs) have been shown to play key roles in tumor progression and metastasis. Results of our preliminary in vitro and in vivo experiments show that miR-451 is upregulated by hypoxia and is involved in glioma angiogenesis. We hypothesize that miR-451 manipulation could block the angiogenic properties of these tumors. Therefore, we will investigate the role of miR-451 in the pro-angiogenic response to hypoxia and test the therapeutic potential of suppressing miR-451 in GBM in vivo. We will determine if miR-451 levels regulate angiogenesis in vitro and in vivo, and attempt to identify the mechanism by which hypoxia-induced miR-451 expression modulates angiogenesis (Fig. 1, see Appendix). To assess the efficacy of an anti-miR-451 approach in inhibiting glioma-associated angiogenesis in vivo, we intend to use the murine GL261 glioma model. Targeting miR-451 might prove to be a powerful therapeutic strategy to inhibit glioma-associated angiogenesis, thus improving the prognosis of GBM patients.
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