HBx and HCV core, viral proteins associated with hepatocarcinoma, promote N-CoR degradation.

Abstract

Hepatocellular carcinoma (HCC) is frequently found in patients with chronic infection of either hepatitis B- or C- virus (HBV or HCV). However, the precise mechanism of how these viral proteins are involved in hepatocarcinogenesis remains unknown. The nuclear receptor co-repressor (N-CoR) and other promyelocytic leukemia oncogenic domain (POD) components have been shown to involve in transcriptional repression function. In this preliminary observation, we detected significant degradation of N-CoR in HBV-containing human hepatoma cell lines. Furthermore, our western blot analyses and localization experiments in 293T (human embryonic kidney) cells demonstrated that hepatitis viral oncogenic proteins, HBV X protein (HBx) and HCV core, disrupted N-CoR-mediated transcriptional repression function by triggering cytosolic localization of N-CoR and its subsequent degradation. Disruption of this biological function suggests the capability of HBV and HCV to overcome the nuclear defense mechanisms exerted by POD which commonly showed structural disintegration in several viral infections. In addition, up-regulation of genes related to cell proliferation in HCC might also be associated with the loss of N-CoR-mediated transcriptional repression activity upon chronic infection by HBV or HCV. Hence, the novel molecular mechanism postulated here can be exploited for therapeutic approaches against HBV and HCV infections and more importantly, in the treatment of HCC.