Tumor Biology

, Volume 37, Issue 8, pp 10375–10382 | Cite as

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

  • Kuan Cao
  • Hui Gong
  • Zhichao Qiu
  • Quan Wen
  • Bin Zhang
  • Tianjin Tang
  • Xinyu Zhou
  • Tong Cao
  • Bin Wang
  • Hengliang Shi
  • Renhao Wang
Original Article

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.

Keywords

HBV HBx ErbB3 Nrdp1 HCC 

Notes

Acknowledgments

This work was supported by the Foundation of Jiangsu Provincial Health Department (H201429), the Foundation of Xuzhou science and Technology Bureau (KC14SX011), the National Natural Science Foundation of China (81201264), the China Postdoctoral Science Foundation (2014 M551662), and the Jiangsu Planned Projects for Postdoctoral Research Funds (1402191C).

Compliance with ethical standards

The study was approved by the research ethics committee.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Kuan Cao
    • 1
    • 3
  • Hui Gong
    • 3
    • 4
  • Zhichao Qiu
    • 3
    • 4
  • Quan Wen
    • 1
  • Bin Zhang
    • 1
  • Tianjin Tang
    • 2
    • 3
  • Xinyu Zhou
    • 1
    • 3
  • Tong Cao
    • 2
    • 3
  • Bin Wang
    • 2
    • 3
  • Hengliang Shi
    • 2
    • 3
  • Renhao Wang
    • 1
  1. 1.Department of general surgeryAffiliated Hospital of Xuzhou Medical CollegeXuzhouChina
  2. 2.Insititute of Nervous System DiseasesXuzhou Medical CollegeXuzhouChina
  3. 3.The Graduate SchoolXuzhou Medical CollegeXuzhouChina
  4. 4.Neurosurgery Department of Jiangsu Haimen People’s HospitalNantongChina

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