Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secreted frizzled-related proteins (SFRPs) are antagonists of the Wnt signaling pathway whose epigenetic downregulation have been shown to be involved in hepatocarcinogenesis. However, dysregulation of SFRPs induced by hepatitis B virus (HBV) X protein (HBx) has never been studied in HBV-related hepatocellular carcinoma (HBV-HCC). In this study, we sought to determine the clinical significance and underlying mechanism of HBx-induced SFRPs dysregulation in hepatoma cells and HBV-HCC patients. Our results showed that SFRP1 and SFRP5 expression were dramatically decreased by HBx in hepatoma cells. The repressed expression in hepatoma cells was partially rescued by a DNA methylation inhibitor and synergistically increased by a combination treatment with a histone deacetyltransferases inhibitor. In addition, we identified that SFRP1 and SFRP5 promoters were hypermethylated in both HBx-expressing hepatoma cells and HBV-HCC tissues. Downregulation of SFRP1 and SFRP5 in HBV-HCC tissues was significantly correlated with overexpression of DNA methyltransferase 1 (DNMT1) and poor tumor differentiation. HBx facilitated the binding of DNMT1 and DNMT3A to SFRP1 and SFRP5 promoters, and resulted in epigenetic silencing of SFRP1 and SFRP5. Moreover, overexpression of SFRP1, SFRP5 or RNA interference mediated silencing of DNMT1 inactivated the Wnt signaling pathway and decreased the expression levels of Wnt target genes c-Myc and CyclinD1, thus impeding HCC growth in vitro and in vivo, and regressing HBx-induced epithelial-mesenchymal transition (EMT). Our findings strongly suggest that epigenetic silencing of SFRP1 and SFRP5 by HBx allows constitutive activation of Wnt signaling pathway and hence contributes to hepatocarcinogenesis.
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PMID:Epigenetic silencing of SFRP1 and SFRP5 by hepatitis B virus X protein enhances hepatoma cell tumorigenicity through Wnt signaling pathway. 2437 50

The aim of this study was to investigate the characteristics of serum secreted frizzled-related protein 5 (SFRP5), an inhibitor of Wnt signaling, in hepatitis B virus (HBV)-associated infections and hepatocellular carcinoma (HCC) patients. Serum SFRP5 levels were detected in 147 patients with HBV-associated chronic infection or HCC. Compared with the non-HBV-infected and non-HCC group, the HBV-associated chronic infection and HCC groups exhibited decreased serum SFRP5 levels. A significant inverse correlation between serum SFRP5 levels and HBV DNA levels was identified in the HBV-associated chronic infection and HCC groups. Furthermore, SFRP5 levels differentially decreased in patients with HBV-associated diseases, in a manner which was dependent on liver disease status. Compared with patients exhibiting HBV-associated chronic infection, patients with HCC were found to exhibit lower serum SFRP5 levels. The results of the present study indicated that patients with HBV-associated liver infection and HCC exhibited significantly deceased serum SFRP5 levels, which were found to negatively correlate with HBV DNA levels. Serum SFRP5 levels may present a biomarker for the severity of HBV-associated liver infection, and the risk of HCC initiation and progression.
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PMID:Serum secreted frizzled-related protein 5 levels differentially decrease in patients with hepatitis B virus-associated chronic infection and hepatocellular carcinoma. 2512 Jul 20