The role of hepatitis B virus X protein in regulation of hypoxia inducible factor-1αand the underlying mechanisms in hepatocellular carcinoma / 中国癌症杂志
China Oncology
;
(12): 333-338, 2015.
Article
in Chinese
| WPRIM
| ID: wpr-463353
ABSTRACT
Background and purpose:
Hepatitis B virus X protein (HBx) and hypoxia inducible factor-1α(HIF-1α) play key roles in hepatocarcinogenesis and the development of hepatocellular carcinoma. Positive correlation on the expression of these 2 proteins in hepatocellular carcinoma tissues has been found, whereas the underlying mechanisms have not been fully elucidated. This study focused on the role of HBx in regulating HIF-1α and the underlying mechanisms in hepatocellular carcinoma cells.Methods:
The expression plasmids were transfected into Huh7 cells with LipofectemineTM 2000. Western blot analysis was applied to detect the expressions of HIF-1αand HIF-1β protein. The transcriptional activity of HIF-1α was detected by the commercial analysis kits. The mRNA levels of HIF-1αand its target genes, including vascular endothelial growth factor (VEGF) and multi-drug resistance gene 1 (MDR1), were detected by quantitative real-time PCR (qRT-PCR). Immunoprecipitation analysis was applied to detect the interaction of HIF-1α, HBx and protein von Hippel-Lindau (pVHL).Results:
Huh7 cells transfected with HBx plasmid led to sharp increase of HIF-1αprotein and transcriptional activity, as well as the mRNA of VEGF and MDR1 (P0.05). Meanwhile, HBx also signiifcantly impaired the function of pVHL in mediating the degradation of HIF-1αby ubiquitin hydrolase. This finding was further confirmed by the immunoprecipitation analysis, which showed that HBx could directly bind to pVHL, but not to HIF-1α.Conclusion:
HBx may inhibit the inter-activation between pVHL and HIF-1αthrough directly binding to pVHL, and thus enhance the stability and transcriptional activity of HIF-1α.
Full text:
Available
Index:
WPRIM (Western Pacific)
Language:
Chinese
Journal:
China Oncology
Year:
2015
Type:
Article
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