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Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System
Published on: December 21, 2019
Activating mechanism of transcriptor NF-kappaB regulated by hepatitis B virus X protein in hepatocellular carcinoma
Tao Wang1, Yi Wang, Meng-Chao Wu
1Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
Aim:
To investigate the mechanism and significance of NF-kappaB activation regulated by hepatitis B virus X protein (HBx) in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).
Methods:
The expression levels of HBx, p65, IkappaB-alpha and ubiquitin were detected by immunohistochemistry in HCC tissue microarrays (TMA) respectively, and IkappaB-alpha was detected by Western blot in HCC and corresponding liver tissues.
Results:
The percentage of informative TMA samples was 98.8% in 186 cases with a total of 367 samples. Compared with corresponding liver tissues (60.0%), the HBx expression was obviously decreased in HBV-associated HCC (47.9%, u=2.24, P<0.05). On the contrary, the expressions of p65 (20.6% vs 45.3%, u=4.85, P<0.01) and ubiquitin (8.9% vs 59.0%, u=9.68, P<0.01) were notably elevated in HCC. In addition, IkappaB-alpha had a tendency to go up. Importantly, positive relativity was observed between HBx and p65 (chi2=10.26, P<0.01), p65 and IkappaB-alpha (chi (2)=16.86, P<0.01), IkappaB-alpha and ubiquitin (chi2=8.90, P<0.01) in HCC, respectively.
Conclusion:
Both active and non-active forms of NF-kappaB are increased in HBV-associated HCC. Variant HBx is the major cause of the enhancement of NF-kappaB activity. The activation always proceeds in nucleus and the proteasome complexes play an important role in the activation.
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