Hepatitis B virus X protein reduces the stability of Nrdp1 to up-regulate ErbB3 in hepatocellular carcinoma cells

• DOI: 10.1007/s13277-016-4936-y
• Publication Date: 2016-02-04T10:00:27Z
• Authors: Kuan Cao; Hui Gong; Zhichao Qiu; Quan Wen; Bin Zhang; Tianjin Tang; Xinyu Zhou; Tong Cao; Bin Wang; Hengliang Shi; Renhao Wang
• Keywords: 0303 health sciences; Carcinoma, Hepatocellular; Receptor, ErbB-3; Ubiquitin-Protein Ligases; Blotting, Western; Liver Neoplasms; Fluorescent Antibody Technique; Cell Transformation, Viral; Hepatitis B; Immunohistochemistry; Up-Regulation; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Trans-Activators; Humans; Immunoprecipitation; Viral Regulatory and Accessory Proteins

Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) is the most widespread type of liver cancer. However, the underlying mechanism of HCC tumorigenesis is very intricate and HBV-encoded X protein (HBx) has been reported to play a key role in this process. It has been reported that HBx up-regulates the transcription of ErbB3. However, it remains unclear whether HBx can regulate ErbB3 expression at post-translational modification level. In this study, we showed that HBx interacts with ubiquitin ligase Nrdp1 (neuregulin receptor degradation protein 1) and decreases its stability, which results in the up-regulation of ErbB3 and promotion of HCC cells. Moreover, the expression of ErbB3 was almost undetectable in normal liver tissues but was relative abundant in HCC tissues, and the level of ErbB3 and Nrdp1 significantly showed a negative correlation in HCC tissues. Taken together, these findings suggest that HBx promotes the progression of HCC by decreasing the stability of Nrdp1, which results in up-regulation of ErbB3, suggesting that ErbB3 may be a target for HCC therapy.