Characterization of metastatic tumor antigen 1 and its interaction with hepatitis B virus X protein in NF-κB signaling and tumor progression in a woodchuck hepatocellular carcinoma model
| Autor: | Hsiu-Lin Lin, Ding-Shinn Chen, C. Wang, Jia-Horng Kao, Huei-Ru Cheng, Chun-Jen Liu, Tung-Hung Su, Hui-Lin Wu, Yung-Ming Jeng, Yung-Tsung Li, Pei-Jer Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Carcinoma
Hepatocellular viruses medicine.disease_cause Transfection 03 medical and health sciences hepatocellular carcinoma (HCC) 0302 clinical medicine Antigen Antigens Neoplasm medicine Animals Humans Viral Regulatory and Accessory Proteins Amino Acid Sequence metastatic tumor antigen 1 (MTA1) Hepatitis B virus biology woodchuck splicing variant business.industry Woodchuck Hepatocellular Carcinoma Woodchuck hepatitis virus Liver Neoplasms NF-kappa B virus diseases HCCS biochemical phenomena metabolism and nutrition NFKB1 biology.organism_classification medicine.disease Virology digestive system diseases Disease Models Animal Oncology Tumor progression hepatitis B virus (HBV) 030220 oncology & carcinogenesis Hepatocellular carcinoma Marmota Cancer research Disease Progression Trans-Activators 030211 gastroenterology & hepatology Female business Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | The metastatic tumor antigen 1 (MTA1) protein is associated with tumor invasiveness and poor prognosis in patients with hepatocellular carcinoma (HCC), particularly in those with hepatitis B virus (HBV)-related HCC. Chronically woodchuck hepatitis virus (WHV)-infected woodchuck is an ideal animal model for studying the pathogenesis of HBV-associated liver diseases, including HCC. To investigate the roles of MTA1 in HBV-associated hepatocarcinogenesis in the woodchuck model, we cloned the woodchuck MTA1 (wk-MTA1) complementary (c)DNA and characterized its molecular functions. The sequence and organization of the wk-MTA1 protein were highly conserved among different species. Similar to its expression in human HCC, wk-MTA1 was upregulated in woodchuck HCC, as determined at RNA and protein levels. Furthermore, an MTA1-spliced variant, wk-MTA1dE4, was overexpressed in woodchuck HCC, and it was attributed to approximately 50% of the total transcripts. The percentage of wk-MTA1dE4-overexpressed woodchuck HCCs was higher than that of the total wk-MTA1-overexpressed HCCs (77.8% vs 61.1%) and wk-MTA1dE4 may represent a more sensitive marker than the total wk-MTA1 in woodchuck HCC. We overexpressed or knocked down wk-MTA1 in a woodchuck HCC cell line and demonstrated that wk-MTA1 could interact with the WHV X protein (WHx) and play indispensable roles in WHx-mediated NF-κB activation and tumor cell migration- and invasion-promoting activities. In conclusion, our results support the hypothesis that woodchuck HCC recapitulates HBV-associated HCC with respect to the molecular characteristics of MTA1 and provides new clues for conducting mechanistic studies of MTA1 in HBV-associated hepatocarcinogenesis, including the possible clinical significance of wk-MTA1dE4. |
| Databáze: | OpenAIRE |
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