iNOS promotes HBx-induced hepatocellular carcinoma via upregulation of JNK activation

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Title
iNOS promotes HBx-induced hepatocellular carcinoma via upregulation of JNK activation
Author(s)
Young-Ho Park; H J Shin; Sun-Uk Kim; J M Kim; J H Kim; D H Bang; Kyu Tae Chang; Bo Yeon Kim; Dae Yeul Yu
Bibliographic Citation
Biochemical and Biophysical Research Communications, vol. 435, no. 2, pp. 244-249
Publication Year
2013
Abstract
Inducible nitric oxide (iNOS) is closely correlated with chronic inflammation in hepatitis B virus X protein (HBx)-induced hepatocellular carcinoma (HCC). However, the molecular mechanisms through which iNOS contribute to hepatocarcinogenesis remain poorly understood. Therefore, we investigated the role of iNOS in signaling pathways underlying HBx-induced liver tumorigenesis. iNOS deletion showed a marked decrease in the hepatic tumor size and stage of HBx transgenic (Tg) mice, indicating a strong contribution of iNOS signaling pathways to hepatocarcinogenesis. In addition, we found that nitric oxide (NO) increased HBx mRNA by recruiting CREB to the CRE site of HBV enhancer in HepG2 cells, suggesting a positive feedback loop between HBx and iNOS signaling pathway. Moreover, iNOS-modulated JNK activation was associated with sustained upregulation of Cyclin D1 in HBxTg mice and HepG2-. HBx cells. These results imply that iNOS may play a key role in HBx-associated HCC development. Taken together, our findings demonstrate that iNOS aligns with HBx to promote tumor progression. These findings provide a better understating of the mechanism involving HBx-mediated hepatic tumorigenesis and selective inhibition of iNOS may have therapeutic applications in HBx-associated HCC.
Keyword
HBxHepatocellular carcinomaINOSJNK
ISSN
0006-291X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bbrc.2013.04.071
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Futuristic Animal Resource & Research Center > 1. Journal Articles
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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