iNOS promotes HBx-induced hepatocellular carcinoma via upregulation of JNK activation
| Autor: | Sun-Uk Kim, Dong-Ho Bang, Kyu-Tae Chang, Young-Ho Park, Hye-Jun Shin, Joo-Hyun Kim, Bo Yeon Kim, Dae-Yeul Yu, Jin-Man Kim |
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| Rok vydání: | 2013 |
| Předmět: |
Carcinoma
Hepatocellular MAP Kinase Kinase 4 viruses Biophysics Nitric Oxide Synthase Type II CREB medicine.disease_cause Biochemistry Nitric oxide chemistry.chemical_compound Mice Cyclin D1 Downregulation and upregulation Cell Line Tumor medicine Animals Viral Regulatory and Accessory Proteins Molecular Biology biology Liver Neoplasms Cell Biology digestive system diseases Up-Regulation Enzyme Activation HBx chemistry Tumor progression Cancer research biology.protein Trans-Activators Signal transduction Carcinogenesis Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 435(2) |
| ISSN: | 1090-2104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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