|Title:||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||Authors:||Li Y.-T.
|Issue Date:||2016||Publisher:||Impact Journals LLC||Journal Volume:||7||Journal Issue:||30||Start page/Pages:||47173-47185||Source:||Oncotarget||Abstract:||
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.
|ISSN:||1949-2553||DOI:||10.18632/oncotarget.9986||SDG/Keyword:||complementary DNA; hepatitis B virus X protein; immunoglobulin enhancer binding protein; metastatic tumor antigen 1; RNA; tumor antigen; unclassified drug; hepatitis B virus X protein; immunoglobulin enhancer binding protein; transactivator protein; tumor antigen; amino acid sequence; animal experiment; animal model; animal tissue; Article; cancer cell culture; cancer growth; cell invasion; cell migration; controlled study; genetic transfection; Hepatitis B virus; hepatocellular carcinoma cell line; immunohistochemistry; liver; liver carcinogenesis; liver cell carcinoma; molecular cloning; nonhuman; Northern blotting; plasmid; protein analysis; protein interaction; reverse transcription polymerase chain reaction; RNA extraction; sequence analysis; upregulation; woodchuck; animal; disease exacerbation; disease model; female; genetics; human; liver cell carcinoma; liver tumor; Marmota; metabolism; pathology; signal transduction; Amino Acid Sequence; Animals; Antigens, Neoplasm; Carcinoma, Hepatocellular; Disease Models, Animal; Disease Progression; Female; Humans; Liver Neoplasms; Marmota; NF-kappa B; Signal Transduction; Trans-Activators; Transfection
|Appears in Collections:||病理學科所|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.