title: Hepatitis B virus X protein reduces the stability of Nrdp1 to up-regulate ErbB3 in hepatocellular carcinoma cells.
abstract: 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.
authors: Department of general surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China.|The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Kuan
authors: K
authors: Cao
authors: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.|Neurosurgery Department of Jiangsu Haimen People's Hospital, Nantong, China.
authors: Hui
authors: H
authors: Gong
authors: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.|Neurosurgery Department of Jiangsu Haimen People's Hospital, Nantong, China.
authors: Zhichao
authors: Z
authors: Qiu
authors: Department of general surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China.
authors: Quan
authors: Q
authors: Wen
authors: Department of general surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China.
authors: Bin
authors: B
authors: Zhang
authors: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.|The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Tianjin
authors: T
authors: Tang
authors: Department of general surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China.|The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Xinyu
authors: X
authors: Zhou
authors: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.|The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Tong
authors: T
authors: Cao
authors: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.|The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Bin
authors: B
authors: Wang
authors: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. shl@xzmc.edu.cn.|The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China. shl@xzmc.edu.cn.
authors: Hengliang
authors: H
authors: Shi
authors: Department of general surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China. wangrenhao@xzmc.edu.cn.
authors: Renhao
authors: R
authors: Wang
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002472:Cell Transformation, Viral / Q000502:physiology; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006509:Hepatitis B / Q000150:complications; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D020893:Receptor, ErbB-3 / Q000096:biosynthesis*; D015534:Trans-Activators / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; C452580:RNF41 protein, human; D044767:Ubiquitin-Protein Ligases; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3
keywords: ErbB3; HBV; HBx; HCC; Nrdp1