Defense Date

2017

Document Type

Thesis

Degree Name

Master of Science

Department

Human Genetics

First Advisor

Devanand Sarkar

Abstract

Astrocyte Elevated Gene 1 (AEG1) is an oncogene for hepatocellular carcinoma (HCC). Its role in HCC pathogenesis has been well studied. A pan cancer analysis of gene expression in multiple databases identified TATA-box binding protein associated factor 2 (TAF2) as the gene that is most frequently co-expressed with AEG1. TAF2 is a protein that is involved in transcription of genes by RNA polymerase II. It is a factor that is dispensable for basal transcription but, required for activated transcription. It has also been shown to be involved in regulating cyclin levels and hence cell cycle progression. Bioinformatic analysis on data from different cancer databases confirmed the positive correlation of TAF2 expression with AEG1 expression, the over expression of TAF2 in HCC patients and poor survival of HCC patients with increasing TAF2. We confirmed the over expression of TAF2 in HCC cell lines using western blotting and HCC liver using immunohistochemistry. We established cell lines with stable knockdown of TAF2 expression. These clones showed significant decrease in their ability to invade and migrate but not their proliferation ability. This is in contrast to what has been observed in previous studies. We hypothesize that the knockdowns do not show any decrease in cellular proliferation since the remaining TAF2 in the cells is sufficient to produce cyclins and keep cell cycle undisturbed. The knockdown of TAF2 causes an increase in E-cadherin level and decrease in Snail protein expression which is a known negative regulator of E-cadherin. Knockdown of TAF2 causes cells to become more epithelial leading to a decrease in their ability to migrate and invade. This study shows that TAF2 is a potential oncogene that needs to be further studied.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

6-16-2017

Available for download on Saturday, June 16, 2018

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