Abstract B30: MicoRNA mediated regulation of antiangiogenic resistance in glioblastoma

Abstract

Abstract Anti-angiogeneic therapies are being used in glioma due to high expression of vascular and angiogenic growth factors but without improved survival and tumor recur. Our study used vatalanib (PTK) in U251 tumor cells which secretes proangiogenic and proinvasive proteins. We found 7 proteins (MMP-2, MMP-9, SDF-1α, Tie-2, MCP-1, IL-8, VE Cadherin, and VEGFA) which were altered greater than 20 fold in both U251 complete medium and lysate. We hypothesized that miRNA regulation may be involved in overexpression of these secreted factors that might be responsible for antiangiogenic resistance in glioma. We performed miRNA profiling (Affymetrix miRNA v3 platform) in U251 glioma cell line treated with or without PTK drug under hypoxia and normoxia conditions. Fold changes were estimated using normoxia group as control against normoxia+PTK, hypoxia, hypoxia+PTK, and changes greater than 5 fold were considered for further analysis to investigate potential targets. We found miR-15a and miR-21 were > 7-fold upregulated in group with hypoxia+PTK treatment. Targetscan analysis showed mir-15a may target TNFAIP3, VEGFA and mir21 can target MMP-2, which were altered in U251 cell lysate. Our present study identified novel microRNAs and gene targets which may lead to antiangiogenic resistance in glioma and provide a basis for future clinical trials. In future, functional assays will confirm the role of candidate miRNAs in tumor vasculature development following antiangiogenic drug treatment. Citation Format: Meenu Jain, Bhagelu Achyut, Adarsh Shankar, Kartik Angara, Asm Iskander, Ali S. Arbab. MicoRNA mediated regulation of antiangiogenic resistance in glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr B30.