Theses and Dissertations

Date of Award

12-2020

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Dr. Megan Keniry

Second Advisor

Dr. Robert Gilkerson

Third Advisor

Dr. Matthew Terry

Abstract

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.

Comments

Copyright 2020 Shreya Udawant. All Rights Reserved.

https://go.openathens.net/redirector/utrgv.edu?url=https://www.proquest.com/dissertations-theses/role-glycolytic-metabolism-glioblastoma/docview/2554455177/se-2?accountid=7119

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