HBx mutants differentially affect the activation of hypoxia-inducible factor-1? in hepatocellular carcinoma.

ABSTRACT: BACKGROUND: Mutations in HBx gene are frequently found in HBV-associated hepatocellular carcinoma (HCC). Activation of hypoxia-inducible factor-1? (HIF-1?) contributes to HCC development and progression. Wild-type HBx has been demonstrated to activate HIF-1?, but the effect of HBx mutations on HIF-1? has not been elucidated. METHODS: HBx mutations were identified by gene sequencing in 101 HCC tissues. Representative HBx mutants were cloned and transfected into HCC cells. Expression and activation of HIF-1? were analysed by western blot and luciferase assays, respectively. The relationship between HBx mutants and HIF-1? expression in HCC tissues was also evaluated. RESULTS: The dual mutations K130M/V131I enhanced the functionality of HBx as they upregulated the expression and transcriptional activity of HIF-1?. The C-terminal truncations and deletion mutations, however, weakened the ability of HBx to upregulate HIF-1?. Meanwhile, the C-terminus was further found to be essential for the stability and transactivation of HBx. In the HCC tissues, there was a positive association between the HBx mutants and HIF-1? expression. CONCLUSION: Different mutations of HBx exert differentiated effects on the functionality of HIF-1?, however, the overall activity of HBx mutants appears to increase the expression and transcriptional activity of HIF-1?.

SUBMITTER: Liu LP 

PROVIDER: S-EPMC3929872 | biostudies-other | 2014 Feb

REPOSITORIES: biostudies-other