Abstract A17: A lincRNA orchestrates glioma stem cell-mediated angiogenesis in glioblastoma

Angiogenesis is a hallmark of glioblastoma. Recent data suggest that glioma stem cells (GSCs) contribute to pathologic angiogenesis through transdifferentiation into endothelial cells or vascular pericytes. Using an unbiased screen, we identified a lincRNA near the VEGFR1 gene, which we named LIVE (lincRNA-VEGFR1), that directs physiologic vascular network formation through global effects on gene expression. LIVE is highly expressed in glioblastoma and enriched in GSCs. Over-expression of LIVE results in specification of GSCs along a vascular lineage. LIVE associates with PARP1 in GSCs and RNA helicase A in endothelial cells to drive pericyte-specific and endothelial-associated gene expression, respectively. Depletion of LIVE in a xenograft model of glioblastoma results in decreased microvascular density, vascular perfusion and pericyte coverage, and depletion of GSCs within the vascular niche. Our findings demonstrate a novel role for lincRNAs in the orchestration of tumour angiogenesis and reveal a therapeutic potential for targeting LIVE in glioblastoma. Citation Format: Jenny J. Wang, Megan Wu, Christopher Li, Uswa Shahzad, Jason Karamchandani, Phil Marsden, Sunit Das. A lincRNA orchestrates glioma stem cell-mediated angiogenesis in glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A17.