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Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
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Hepatitis B virus X protein and hypoxia‑inducible factor-1α stimulate Notch gene expression in liver cancer cells

Sheng-Li Yang1, Quan-Guang Ren1, Tao Zhang1

  • 1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

Oncology Reports
|November 15, 2016
PubMed

Insights

Notch1, Notch3, and Notch4 genes are upregulated in hepatocellular carcinoma (HCC) tissues. Hepatitis B virus X protein (HBx) and hypoxia-inducible factor-1α (HIF-1α) may drive this overexpression, with Notch3 linked to tumor invasiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Hepatology

Background:

  • Notch genes are implicated in carcinogenesis, but their specific roles in hepatocellular carcinoma (HCC) require further elucidation.
  • Understanding Notch gene expression and regulation in HCC is crucial for identifying potential therapeutic targets.

Purpose of the Study:

  • To investigate the expression levels of Notch1, Notch2, Notch3, and Notch4 in HCC tissues compared to normal and peritumoral liver tissues.
  • To explore the regulatory roles of hepatitis B virus X protein (HBx) and hypoxia-inducible factor-1α (HIF-1α) in Notch gene expression within HCC.
  • To determine the correlation between Notch gene expression and clinicopathological features of HCC, specifically vascular invasion.

Main Methods:

  • Immunohistochemistry and quantitative real-time PCR (qPCR) were used to assess Notch gene expression in tissue samples.
  • qPCR and western blotting were employed to study the effects of HBx and HIF-1α overexpression on Notch gene expression in liver cell lines.
  • Statistical analyses were performed to correlate gene expression with clinicopathological data.

Main Results:

  • Notch1, Notch3, and Notch4 showed significantly higher expression in HCC tissues compared to peritumoral and normal liver tissues.
  • Notch2 expression did not significantly differ between HCC and peritumoral tissues.
  • Overexpression of HBx and HIF-1α led to increased expression of Notch1, Notch3, and Notch4 in HepG2 and Bel-7404 cell lines.
  • Elevated Notch3 levels in HCC tissues were positively correlated with vascular invasion.

Conclusions:

  • Notch1, Notch3, and Notch4 are upregulated in HCC, suggesting their involvement in HCC development.
  • HBx and HIF-1α are potential regulators contributing to the overexpression of Notch genes in HCC.
  • Notch3 upregulation is associated with increased vascular invasiveness in HCC, highlighting its clinical significance.

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