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Basic Characteristics of Mutations
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Mutation Site
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H86Y |
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Mutation Site Sentence
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To this end, six artificial HBx mutants have been established, including HA-A12T-HBx, HA-V44I-HBx, HA-A66T-HBx, HA-H86Y-HBx, HA-E109D-HBx and HA-K130M/V131I-HBx (Figure 1A). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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X |
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Standardized Encoding Gene
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X
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Carcinoma, Hepatocellular
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Immune
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- |
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Target Gene
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HIF1A
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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24346287
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Title
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HBx mutants differentially affect the activation of hypoxia-inducible factor-1alpha in hepatocellular carcinoma
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Author
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Liu LP,Hu BG,Ye C,Ho RL,Chen GG,Lai PB
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Journal
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British journal of cancer
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Journal Info
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2014 Feb 18;110(4):1066-73
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Abstract
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BACKGROUND: Mutations in HBx gene are frequently found in HBV-associated hepatocellular carcinoma (HCC). Activation of hypoxia-inducible factor-1alpha (HIF-1alpha) contributes to HCC development and progression. Wild-type HBx has been demonstrated to activate HIF-1alpha, but the effect of HBx mutations on HIF-1alpha 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-1alpha were analysed by western blot and luciferase assays, respectively. The relationship between HBx mutants and HIF-1alpha 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-1alpha. The C-terminal truncations and deletion mutations, however, weakened the ability of HBx to upregulate HIF-1alpha. 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-1alpha expression. CONCLUSION: Different mutations of HBx exert differentiated effects on the functionality of HIF-1alpha, however, the overall activity of HBx mutants appears to increase the expression and transcriptional activity of HIF-1alpha.
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Sequence Data
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-
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