A mutant of hepatitis B virus X protein (HBxDelta127) promotes cell growth through a positive feedback loop involving 5-lipoxygenase and fatty acid synthase.

Neoplasia : an International Journal for Oncology Research
Qi WangXiaodong Zhang

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Hepatitis B virus X protein (HBx) contributes to the development of HCC, whereas HBx with COOH-terminal deletion is a frequent event in the HCC tissues. Previously, we identified a natural mutant of HBx-truncated 27 amino acids at the COOH-terminal (termed HBxDelta127), which strongly enhanced cell growth. In the present study, we focused on investigating the mechanism. Accordingly, fatty acid synthase (FAS) plays a crucial role in cancer cell survival and proliferation; thus, we examined the signaling pathways involving FAS. Our data showed that HBxDelta127 strongly increased the transcriptional activities of FAS in human hepatoma HepG2 and H7402 cells. Moreover, we found that 5-lipoxygenase (5-LOX) was responsible for the up-regulation of FAS by using MK886 (an inhibitor of 5-LOX) and 5-LOX small interfering RNA. We observed that HBxDelta127 could upregulate 5-LOX through phosphorylated extracellular signal-regulated protein kinases 1/2 and thus resulted in the increase of released leukotriene B4 (LTB4, a metabolite of 5-LOX) by ELISA. The additional LTB4 could upregulate the expression of FAS in the cells as well. Interestingly, we found tha...Continue Reading

Citations

Jan 14, 2011·Journal of Gastroenterology and Hepatology·Michael C Kew
Aug 2, 2011·Acta Pharmacologica Sinica·Guang-yao KongXiao-dong Zhang
Apr 30, 2017·Biological Chemistry·Thomas TuRalf Bartenschlager
Jun 8, 2011·Journal of Gastroenterology·Sue-Ann Ng, Caroline Lee
Aug 19, 2014·World Journal of Gastroenterology : WJG·Ashraf AliIshtiaq Qadri
Oct 20, 2015·World Journal of Gastroenterology : WJG·Ming GengXiao-Hong Liu
Jul 8, 2017·Archives of Virology·Muhammad DaudBushra Ijaz
Apr 11, 2017·Viruses·Thomas TuStephan Urban
Nov 15, 2015·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Lei LiYoungho Seo
Dec 14, 2018·Oxidative Medicine and Cellular Longevity·Serena De MatteisAnna Maria Giudetti
Nov 8, 2018·Gastroenterology·Renumathy DhanasekaranJessica Zucman-Rossi

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