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Article

Hepatitis B virus X protein and hypoxia‑inducible factor-1α stimulate Notch gene expression in liver cancer cells

  • Authors:
    • Sheng-Li Yang
    • Quan-Guang Ren
    • Tao Zhang
    • Xiaoli Pan
    • Lu Wen
    • Jian-Li Hu
    • Chao Yu
    • Qian-Jin He
  • View Affiliations / Copyright

    Affiliations: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Gastroenterology and Hepatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550001, P.R. China, Department of General Surgery, Huanggang Central Hospital, Huanggang, Hubei 438000, P.R. China
  • Pages: 348-356
    |
    Published online on: November 2, 2016
       https://doi.org/10.3892/or.2016.5211
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Abstract

Increasing evidence has demonstrated that Notch genes, including Notch1, Notch2, Notch3 and Notch4, are involved in carcinogenesis. However, the expression and regulation of Notch genes in hepatocellular carcinoma (HCC) tissues have not been fully investigated. In the present study, immunohistochemical and quantitative real-time PCR (qPCR) analyses were performed to examine the expression of Notch genes in normal human liver, HBV-related HCC and paired peritumoral tissues. Additionally, qPCR and western blotting were utilized to investigate the impact of hepatitis B virus X protein (HBx) and hypoxia‑inducible factor-1α (HIF-1α) on the regulation of Notch gene expression. The immunohistochemical and qPCR results showed that the expression levels of Notch1, Notch3 and Notch4 were significantly higher in HCC tissues than the levels in peritumoral and normal liver tissues. However, no significant difference in Notch2 expression was found between HCC and peritumoral tissues. Among the four Notch genes, immunohistochemical analyses found that only the increased level of Notch3 in HCC tissues was positively correlated with vascular invasion of liver cancer (P<0.05). Moreover, we found that overexpression of both HBx and HIF-1α increased the expression of Notch1, Notch3 and Notch4 in HepG2 and Bel-7404 cell lines. In summary, the present study demonstrated that Notch1, Notch3 and Notch4 were upregulated in HCC tissues and that HBx and HIF-1α may be the factors that cause the overexpression of Notch genes. Furthermore, the increased expression of Notch3 was closely related to the vascular invasiveness of HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Yang S, Ren Q, Zhang T, Pan X, Wen L, Hu J, Yu C and He Q: Hepatitis B virus X protein and hypoxia‑inducible factor-1α stimulate Notch gene expression in liver cancer cells. Oncol Rep 37: 348-356, 2017.
APA
Yang, S., Ren, Q., Zhang, T., Pan, X., Wen, L., Hu, J. ... He, Q. (2017). Hepatitis B virus X protein and hypoxia‑inducible factor-1α stimulate Notch gene expression in liver cancer cells. Oncology Reports, 37, 348-356. https://doi.org/10.3892/or.2016.5211
MLA
Yang, S., Ren, Q., Zhang, T., Pan, X., Wen, L., Hu, J., Yu, C., He, Q."Hepatitis B virus X protein and hypoxia‑inducible factor-1α stimulate Notch gene expression in liver cancer cells". Oncology Reports 37.1 (2017): 348-356.
Chicago
Yang, S., Ren, Q., Zhang, T., Pan, X., Wen, L., Hu, J., Yu, C., He, Q."Hepatitis B virus X protein and hypoxia‑inducible factor-1α stimulate Notch gene expression in liver cancer cells". Oncology Reports 37, no. 1 (2017): 348-356. https://doi.org/10.3892/or.2016.5211
Copy and paste a formatted citation
x
Spandidos Publications style
Yang S, Ren Q, Zhang T, Pan X, Wen L, Hu J, Yu C and He Q: Hepatitis B virus X protein and hypoxia‑inducible factor-1α stimulate Notch gene expression in liver cancer cells. Oncol Rep 37: 348-356, 2017.
APA
Yang, S., Ren, Q., Zhang, T., Pan, X., Wen, L., Hu, J. ... He, Q. (2017). Hepatitis B virus X protein and hypoxia‑inducible factor-1α stimulate Notch gene expression in liver cancer cells. Oncology Reports, 37, 348-356. https://doi.org/10.3892/or.2016.5211
MLA
Yang, S., Ren, Q., Zhang, T., Pan, X., Wen, L., Hu, J., Yu, C., He, Q."Hepatitis B virus X protein and hypoxia‑inducible factor-1α stimulate Notch gene expression in liver cancer cells". Oncology Reports 37.1 (2017): 348-356.
Chicago
Yang, S., Ren, Q., Zhang, T., Pan, X., Wen, L., Hu, J., Yu, C., He, Q."Hepatitis B virus X protein and hypoxia‑inducible factor-1α stimulate Notch gene expression in liver cancer cells". Oncology Reports 37, no. 1 (2017): 348-356. https://doi.org/10.3892/or.2016.5211
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