Date of Award
Master of Science (MS)
Dr. Megan Keniry
Dr. Robert Gilkerson
Dr. Matthew Terry
PI3K/AKT/mTOR signaling pathway is activated in 90% of all Glioblastoma Multiforme (GBM) tumors. We used a dual targeting approach to interfere with the phosphoinositide 3-kinase- mammalian target of rapamycin (PI3K-mTOR) pathway by treating U87MG GBM cells with NVP-BEZ235 (PI3K and mTOR a dual inhibitor) and, their downstream effects on molecular regulation on glycolytic genes were investigated using RNA-sequencing and gene set enrichment analysis (GSEA). RNA-seq identified 7803 differentially regulated genes in response to NVP-BEZ235. GSEA identified two glycolysis-related gene sets had significant differences (P < 0.05) in gene expression between control and NVP-BEZ235 treated samples. The GSEA core enrichment reported 17 and 35 genes were significantly downregulated (P adj < 0.05) in response to NVP-BEZ235 treatment in two different glycolysis related gene sets. We validated the expression of genes using qRT-PCR in U87MG cells as well as other GBM cell lines. Our results suggest novel insights on hallmark metabolic reprogramming associated with the PI3K-mTOR inhibition and provides advances in developing molecular targeted therapies.
Udawant, Shreya, "Role of Glycolytic Metabolism in Glioblastoma Multiforme" (2020). Theses and Dissertations. 783.
Available for download on Saturday, September 30, 2023