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

  • Published online on: November 2, 2016     https://doi.org/10.3892/or.2016.5211
  • Pages: 348-356
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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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January-2017
Volume 37 Issue 1

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

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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