Date of Award

2025

Embargo Period

8-6-2030

Document Type

Thesis - MUSC Only

Degree Name

Master of Science (MS)

Department

Biomedical Sciences

Additional Department

Cell and Molecular Pharmacology and Experimental Therapeutics

College

College of Graduate Studies

First Advisor

Joe B. Blumer

Second Advisor

Scott T. Eblen

Third Advisor

Haizhen Wang

Fourth Advisor

Daniel Gioeli

Abstract

Ovarian cancer is the most lethal gynecological cancer and one of the leading causes of cancer-related deaths. In the United States, it is estimated that over 20,000 new cases and over 12,000 deaths will occur in 2025. The high mortality rate can be attributed to both acquired drug resistance and metastasis. The study of metastatic ovarian cancer is necessary to determine novel mechanisms that can be targeted to improve the standard of care for ovarian cancer. We have previously shown that the E3 ubiquitin ligase UBR5 promotes cisplatin resistance in ovarian cancer cells and xenografts. Proteomic screening revealed a novel substrate of UBR5 that has been associated with ovarian cancer progression. In this study, we hypothesize that UBR5 promotes proteasomal degradation of this novel substrate concomitant with an additional oncogene to facilitate ovarian cancer metastasis. To elucidate this mechanism, we performed gene knockout or knockdown in an ovarian cancer metastasis model to assess the effects on cell morphology, proliferation, and gene and protein expression by using imaging, cell viability assay, RT-qPCR, and immunoblotting. Our results demonstrate a novel role of UBR5 in promoting proteasomal degradation of two substrates in ovarian cancer metastasis and suggest a novel gene regulatory mechanism that may contribute to metastasis in ovarian cancer.

Rights

Copyright is held by the author. All rights reserved.

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Available for download on Tuesday, August 06, 2030

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