Hepatitis B virus induces hypoxia-inducible factor-2α expression through hepatitis B virus X protein

  • Authors:
    • Jian‑Li Hu
    • Li‑Ping Liu
    • Sheng‑Li Yang
    • Xiefan Fang
    • Lu Wen
    • Quan‑Guang Ren
    • Chao Yu
  • View Affiliations

  • Published online on: December 8, 2015     https://doi.org/10.3892/or.2015.4480
  • Pages: 1443-1448
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Abstract

A growing number of studies suggest that the hepatitis B virus X protein (HBx) enhances the protein stability of the hypoxia-inducible factor-1α (HIF-1α). However, the relationship between hepatitis B virus (HBV), HBx and hypoxia-inducible factor-2α (HIF-2α) has not yet been fully elucidated. Immunohistochemical analysis was employed to detect the expression of HIF-2α in normal liver, HBV-related chronic hepatitis, and HBV-related and non-HBV-related hepatocellular carcinoma (HCC) tissues. Quantitative real‑time PCR (qPCR) and western blotting were used to investigate the impact of HBV and HBx on the expression of HIF‑2α. Immunoprecipitation and immunofluorescence were applied to explore the underlying mechanisms. The HIF‑2α expression was found to be higher in HBV‑related chronic hepatitis tissues than in normal liver tissues. Furthermore, it was higher in HBV‑related HCC tissues and HBV‑integrated HepG2 cells than in the corresponding non‑HBV‑related HCC tissues and HepG2 cells. Both HBV and HBx enhanced the protein stability of HIF‑2α. HBx‑mediated upregulation of HIF‑2α resulted mainly from an inhibition of the degradation of HIF‑2α due to the binding of HBx to the von Hippel‑Lindau protein (pVHL). In addition, HBx upregulated the expression of HIF‑2α by activating the NF‑κB signaling pathway. Thus, the present study identified that HBV induces the HIF‑2α expression through its encoded protein HBx. This upregulates the HIF-2α expression by binding to the pVHL activating the NF-κB signaling pathway.
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March-2016
Volume 35 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Hu JL, Liu LP, Yang SL, Fang X, Wen L, Ren QG and Yu C: Hepatitis B virus induces hypoxia-inducible factor-2α expression through hepatitis B virus X protein. Oncol Rep 35: 1443-1448, 2016
APA
Hu, J., Liu, L., Yang, S., Fang, X., Wen, L., Ren, Q., & Yu, C. (2016). Hepatitis B virus induces hypoxia-inducible factor-2α expression through hepatitis B virus X protein. Oncology Reports, 35, 1443-1448. https://doi.org/10.3892/or.2015.4480
MLA
Hu, J., Liu, L., Yang, S., Fang, X., Wen, L., Ren, Q., Yu, C."Hepatitis B virus induces hypoxia-inducible factor-2α expression through hepatitis B virus X protein". Oncology Reports 35.3 (2016): 1443-1448.
Chicago
Hu, J., Liu, L., Yang, S., Fang, X., Wen, L., Ren, Q., Yu, C."Hepatitis B virus induces hypoxia-inducible factor-2α expression through hepatitis B virus X protein". Oncology Reports 35, no. 3 (2016): 1443-1448. https://doi.org/10.3892/or.2015.4480