Date of Award

Summer 2024

Language

English

Embargo Period

8-9-2024

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Biomedical Sciences

Program

Biomedical Sciences

First Advisor

Jason Herschkowitz

Committee Members

Jason Herschkowitz, Douglas Conklin, Sridar Chittur, Daniel Fabris

Abstract

Breast cancer is a complex disease that continues to haunt women and their loved ones around the world. It is currently the leading cause of cancer-related mortality among women. While most breast cancer patients can catch the disease before progression, others are less fortunate. The prognosis of those whose disease has advanced to metastatic or invasive breast cancer (IBC) is grim. Metastasis occurs when cancer cells undergo epithelial to mesenchymal transition (EMT), migrate to distant body tissues, then form new tumors. It is imperative to better understand the process of EMT to develop superior ways to detect breast cancer before becoming metastatic. Recently, post-transcriptional modifications have been implicated in the regulation of EMT in different cancer types. Previous studies lead us to believe that N4-actylcytidine may be involved in the process of EMT in human breast cancer. N4-actylcytidine (ac4C) is produced by the enzyme N-acetyltransferase 10 (NAT10). To establish an understanding of ac4C’s role, we conducted several experiments while altering the expression of NAT10 in Human Mammary Epithelial (HMLE) cells. In this study, we show that the overexpression of NAT10 in HMLE cells induces certain characteristics of the mesenchymal phenotype. We also confirm a proposed method of ac4C-seq by confirming one N4-acetylcytidine site (C-1842) on the 18S ribosome of HMLE cells. These results help us to better understand the role of ac4C in the process of EMT in human breast cancer which may help to pave the way for better preventative interventions and treatments for patients with metastatic breast cancer.

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