Theses and Dissertations

Date of Award

5-2021

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

The PI3K/AKT/mTOR pathway regulates important cell processes such as growth, survival, motility, inflammation, proliferation, and apoptosis. In Glioblastoma multiforme (GBM) the PI3K/AKT/mTOR pathway is aberrant as it is almost always active. This results in the deregulation of downstream molecules and ultimately leads to cancer progression and maintenance in GBM tumors. In this study, we used RNA-sequencing to identify differentially expressed genes (DEGs) in U87MG GBM cells treated with NVP-BEZ235, a dual inhibitory drug targeting PI3K and mTOR. A total of 7,803 differentially expressed genes were identified via RNA-seq. GEPIA2 online tool was used to assess differential gene expression significance in clinical GBM tumors compared to normal control samples. We also validated the expression of five DEGs, including BMP7, in five GBM cell lines using q-RT-PCR. We treated U87MG cells with drugs targeting the PI3K/AKT/mTOR pathway and found no evidence that BMP7 gene expression is directly regulated by FOXO 1. However, BMP7 was associated with several differentially expressed genes in U87MG cells in response to NVP-BEZ235. Thus, we conclude that BMP7 expression and regulation should be studied to ultimately find novel genes for targeted drug therapies for GBM treatments.

Comments

Copyright 2021 Yajaira Janett Macias. All Rights Reserved.

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