Advisor(s)
Zhangli Su
Committee Member(s)
Anindya Dutta
Fengbin Wang
School
Joint Health Sciences (Interdisciplinary)
Document Type
Thesis
Department (new version)
Joint Health Sciences
Date of Award
9-11-2025
Abstract
Glioblastoma (GBM) is a fast growing and highly aggressive brain tumor that affects over 14,000 Americans each year. These tumors are so aggressive that only ~6.8% of patients will live five or more years post-diagnosis. A massive challenge faced when treating GBM is chemoresistance to the main chemotherapy drug used, temozolomide (TMZ). TMZ is an alkylating agent that could trigger RNA alkylation damage in addition to the well-known DNA alkylation damage. Our research aims to explore TMZ-induced RNA damage to determine if RNA methylation contributes to GBM chemoresistance. To understand whether TMZ alkylates RNA substrates and how this alkylation affects global translation in GBM cells, we used two systems: in vitro translation followed by luciferase assay and puromycin labeling in GBM cells followed by western blot. We found TMZ-treatment decreased translation by both assays and also saw increases in levels of specific RNA modifications. We then tested if over-expression of RNA repair/eraser enzymes alters global translation and TMZ responsiveness using cell viability assay. We successfully created four GBM cell lines that express an RNA- specific repair enzyme and its catalytic mutant with and without a nuclear localization signal (NLS), allowing us to distinguish cytoplasmic effects from nuclear effects. Introducing RNA repair enzyme with no NLS to U251 GBM cells decreased translation and cell proliferation, suggesting that the increase in expression of RNA erasers removes RNA modifications that increase cell viability and are potential contributors to the chemoresistance seen in TMZ-resistant GBM. These results implicate TMZ-induced RNA damage as a contributor to chemoresistance. Exploring this relationship further will expand our knowledge of RNA’s role in cancer and help create better treatment options for patients suffering with GBM.
ProQuest ID
Recommended Citation
Rhodes, Jayden Alyse, "The Role Of Rna Alkylation In The Temozolomide Response Of Glioblastoma" (2025). All ETDs from UAB. 7367.
https://digitalcommons.library.uab.edu/etd-collection/7367
