IDENTIFYING THE ROLE OF TIP60 IN HEPATOCELLULAR CARCINOMA

Abstract

TIP60 is a lysine acetyltransferase that is known to be destabilized by different oncoviruses. I investigated the role of TIP60 in HBV-induced Hepatocellular Carcinoma, which is the primary malignancy of the liver and accounts for high mortality rate. It was observed that TIP60, a tumor suppressor implicated in multiple cancers, is downregulated in cells expressing HBx, an oncogene of HBV. This was through a proteasomal mechanism such that HBx utilizes an E3 ubiquitin ligase, EDD1/UBR5 to destabilize TIP60. In inflammation induced liver cancer, I found that TIP60 plays a role in modulating innate immune response by its ability to regulate various interferon factors as well as different cytokines and chemokines. Using an in vitro model, TIP60 was found to inhibit the invasion potential of liver cancer cells. These data show an unidentified role of TIP60 in HBV-induced HCC carcinogenesis and provides promising strategies towards therapeutic avenues in liver cancer.