Hepatitis B virus (HBV) infection is a prominent cause of hepatocellular carcinoma (HCC) but the underlying molecular mechanisms are complex and multiple pathways have been proposed such as the activation of the Wnt-/β-catenin-signalling and dysregulation of E-cadherin/β-catenin adherens junctions.
Expression levels of 250 miRNAs in 46 benign and malignant hepatocellular tumors were compared to those of 4 normal liver samples with quantitative reverse-transcriptase polymerase chain reaction. miRNAs associated with genetic and clinical characteristics were validated in a second series of 43 liver tumor samples and 16 nontumor samples. miRNA profiling unsupervised analysis classified samples in unique clusters characterized by histological features (tumor/nontumor, P < 0.001; benign/malignant tumors, P < 0.01; inflammatory adenoma and focal nodular hyperplasia, P < 0.01), clinical characteristics [hepatitis B virus (HBV) infection, P < 0.001; alcohol consumption, P < 0.05], and oncogene/tumor suppressor gene mutations [beta-catenin, P < 0.01; hepatocyte nuclear factor 1alpha (HNF1alpha), P < 0.01].
Genetic polymorphisms in the Wnt/β-catenin pathway genes as predictors of tumor development and survival in patients with hepatitis B virus-associated hepatocellular carcinoma.
Here, it was demonstrated that hepatitis B virus X protein (HBx) differentially regulates the level of beta-catenin through two ubiquitin-dependent proteasome pathways depending on p53 status.
In our study, we screened HCCs resulting from HCV infection (51 cases), HBV infection (26 cases) or excess alcohol intake (23 cases) for alterations in genes involved in the RB1 pathway (p16(INK4a), p15(INK4b), RB1, CDK4 and cyclin D1), the p53 pathway (p53, p14(ARF) and MDM2) and the Wnt pathway (beta-catenin, APC).
In this study, we used the promiscuous murine cytomegalovirus promoter, a chimeric regulatory sequence consisting of the hepatitis B virus enhancer II and the human alpha1-antitrypsin (EII-Pa1AT) promoter, and a synthetic regulatory sequence consisting of a series of T-cell factor binding sites named the CTP4 promoter to generate replicating MLV vectors, whereby the last two are transcriptionally restricted to liver- and beta-catenin/T-cell factor-deregulated cells, respectively.
Serum levels of β-catenin, from 77 patients with chronic hepatitis B (CHB), 63 patients with hepatitis B associated liver cirrhosis (HBLC), 61 patients with hepatocellular carcinoma (HCC), 41 healthy HBV carriers (HHCs) and 78 healthy controls (HCs) were measured by ELISA.
TERT and CTNNB1 mutations were found more frequently in HCV related (53.6% and 26.4%, respectively) than HBV related (41.7% and 16.7%, respectively) HCCs and coexisted in 57.6% of CTNNB1 mutated tumors.
There was a relationship between the expression of beta-catenin and hepatitis B virus (HBV) infection in the adjacent liver tissues in Guangxi, and between the expression of beta-catenin and p53 in HCC tissues in Malaysia.
Through this phosphorylation-dependent prolyl isomerization, PIN1 fine-tunes the functions of key phosphoproteins (<i>e.g</i>., cyclin D1, survivin, β-catenin and x-protein of hepatitis B virus) that are involved in the regulation of cell cycle progression, apoptosis, proliferation and oncogenic transformation.
Unlike hepatocellular carcinomas in China, Japan, and Europe, deregulating beta-catenin gene mutations do not appear to occur in southern African Blacks with this tumor and do not therefore interact with either the 249serine p53 gene mutation or hepatitis B virus infection in its pathogenesis.
Upregulated gene 11 (URG11), a new gene upregulated by Hepatitis B Virus X protein (HBx), was previously shown to activate beta-catenin and promote hepatocellular growth and tumourigenesis.