![]() ![]() HBx also directly interacts with components of the basal transcription machinery, such as ribosome-binding protein 5, TATA-binding protein, and the transcriptional activator CREB/ATF to regulate gene expression ( 9– 11). Several responsive elements are involved in the transactivation of HBx, including AP-1, NF-κ B, and HIF-1. Many studies have demonstrated that HBx regulates viral gene expression by transactivating the enhancers of HBV and also mediates the expression of cellular genes in infected cells to facilitate tumorigenesis ( 5– 8). ![]() HBx is a multifunctional protein that activates many viral and cellular genes, modulates cellular signal transduction pathways, and regulates cell proliferation and apoptosis ( 4). It has been reported that the X protein (HBx) of HBV plays a crucial role in hepatocarcinogenesis ( 3). However, the complex mechanism by which HBV infection leads to the development of HCC mostly remains unclear. Among them, 400 million are chronically infected ( 2). ![]() Such infection remains a major health problem with 2 billion people infected worldwide. Hepatitis B virus (HBV) 3 infection can cause severe liver diseases, including chronic hepatitis and hepatocellular carcinoma (HCC) ( 1). These findings should provide new insights into our understanding how the molecular mechanisms underline the effects of HBV infection on the production of MAT2A and the development of HCC. Thus, we proposed that HBx activates MAT2A expression through NF-κ B and CREB signaling pathways to reduce AdoMet production, inhibit hepatoma cell apoptosis, and perhaps enhance HCC development. Furthermore, we demonstrated that HBx reduces M AT1A expression and AdoMet production but enhances MAT2β expression. In addition, overexpression of HBx or MAT2A inhibits cell apoptosis, whereas knockdown of MAT2A expression stimulates apoptosis in hepatoma cells. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) further demonstrated that HBx facilitates the binding of NF-κ B and CREB to MAT2A gene promoter. Our in vitro results revealed that HBx activates MAT2A expression in a dose-dependent manner in hepatoma cells, and such regulation requires the cis-regulatory elements NF-κ B and CREB on the MAT2A gene promoter. Results from immunohistochemistry analyses of 37 pairs of HBV-associated liver cancer tissues/corresponding peritumor tissues showed that HBx and MAT2A are highly expressed in most liver tumor tissues. In this study, the effects of HBx on MAT2A expression and cell apoptosis were investigated, and the molecular mechanism by which HBx and MAT2A regulate tumorigenesis was evaluated. Thus, we speculated that a link between HBx and MAT2A may contribute to HCC development. The X protein (HBx) of hepatitis B virus (HBV) is involved in the development of hepatocellular carcinoma (HCC), and methionine adenosyltransferase 2A ( MAT2A) promotes the growth of liver cancer cells through altering S-adenosylmethionine homeostasis. ![]()
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