Theses and Dissertations

Date of Award

5-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biochemistry and Molecular Biology

First Advisor

Manish Tripathi

Second Advisor

Nirakar Sahoo

Third Advisor

Yonghong Zhang

Abstract

Hepatocellular carcinoma (HCC) is the most common liver cancer, with early-stage cases potentially benefiting from surgical treatments like liver transplantation and hepatectomy. However, advanced HCC stages have poor prognosis due to resistance to therapies, especially sorafenib, a tyrosine kinase inhibitor approved for late-stage HCC. Despite its clinical use, sorafenib has limited efficacy in prolonging survival, and the mechanisms of resistance remain unclear. Analysis of The Cancer Genome Atlas (TCGA) HCC dataset shows elevated Y-box binding protein 1 (YBX1) expression in HCC tumors compared to normal liver tissues. Previous studies have indicated that YBX1 is involved in drug resistance in various cancers, including breast and colorectal cancers. This study demonstrates that YBX1 overexpression contributes to sorafenib resistance in HCC. Overexpression of YBX1 in HCC cell lines increased cell survival, viability, and sorafenib IC50 values, along with enhanced tumorigenic traits such as invasion, migration, and proliferation. In contrast, siRNA-mediated knockdown of YBX1 reduced these effects. Additionally, RNA analysis of sorafenib-resistant cells showed upregulation of YBX1 and drug resistance markers such as CD44, MDR1 and PDL1. YBX1 inhibition significantly decreased cell viability. These results suggest that YBX1 mediates sorafenib resistance, contributing to disease progression and poor prognosis, making it a potential therapeutic target in HCC.

Comments

Copyright 2025 Dennis Kwabiah. https://proquest.com/docview/3240612190

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