Activating mechanism of transcriptor NF-kappaB regulated by hepatitis B virus X protein in hepatocellular carcinoma

AIM:To investigate the mechanism and significance ofNF-kB activation regulated by hepatitis B virus X protein(HBx)in hepatitis B virus(HBV)-associated hepatocellularcarcinoma(HCC).METHODS:The expression levels of HBx,p65,IkB-α andubiquitin were detected by immunohistochemistry in HCCtissue microarrays(TMA)respectively,and IkB-α was detectedby Western blot in HCC and corresponding liver tissues.RESULTS:The percentage of informative TMA samples was98.8% in 186 cases with a total of 367 samples.Comparedwith corresponding liver tissues(60.0%),the HBx expressionwas obviously decreased in HBV-associated HCC(47.9%,u=2.24,P<0.05).On the contrary,the expressions of p65(20.6% vs45.3%,u=4.85,P<0.01)and ubiquitin(8.9% vs59.0%,u=9.68,P<0.01)were notably elevated in HCC.Inaddition,IkB-α had a tendency to go up.Importantly,positiverelativity was observed between HBx and p65(x~2=10.26,P<0.01),p65 and IkB-α(x~2=16.86,P<0.01),IkB-α andubiquitin(x~2=8.90,P<0.01)in HCC,respectively.CONCLUSION:Both active and non-active forms of NF-kBare increased in HBV-associated HCC.Variant HBx is themajor cause of the enhancement of NF-kB activity.Theactivation always proceeds in nucleus and the proteasomecomplexes play an important role in the activation.