Hepatocellular carcinoma (HCC), is the third leading cause of cancer-related deaths, which is largely caused by virus infection. About 80% of the virus-infected people develop a chronic infection that eventually leads to liver cirrhosis and hepatocellular carcinoma (HCC). With approximately 71 million HCV chronic infected patients worldwide, they still have a high risk of HCC in the near future. However, the mechanisms of carcinogenesis in chronic HCV infection have not been still fully understood, which involve a complex epigenetic regulation and cellular signaling pathways. Here, we summarize 18 specific gene targets and different signaling pathways involved in recent findings. With these epigenetic alterations requiring histone modifications and DNA hyper or hypo-methylation of these specific genes, the dysregulation of gene expression is also associated with different signaling pathways for the HCV life cycle and HCC. These findings provide a novel insight into a correlation between HCV infection and HCC tumorigenesis, as well as potentially preventable approaches. Hepatitis C virus (HCV) infection largely causes hepatocellular carcinoma (HCC) worldwide with 3 to 4 million newly infected cases diagnosed each year. It is urgent to explore its underlying molecular mechanisms for therapeutic treatment and biomarker discovery. However, the mechanisms of carcinogenesis in chronic HCV infection have not been still fully understood, which involve a complex epigenetic regulation and cellular signaling pathways. Here, we summarize 18 specific gene targets and different signaling pathways involved in recent findings. With these epigenetic alterations requiring histone modifications and DNA hyper or hypo-methylation of these specific genes, the dysregulation of gene expression is also associated with different signaling pathways for the HCV life cycle and HCC. These findings provide a novel insight into a correlation between HCV infection and HCC tumorigenesis, as well as potentially preventable approaches.
Transcription factors directly regulate gene expression by recognizing and binding to specific DNA sequences, involving the dynamic alterations of chromatin structure and the formation of a complex with different kinds of cofactors, like DNA/histone modifying-enzymes, chromatin remodeling factors, and cell cycle factors. Despite the significance of transcription factors, it remains unclear to determine how these cofactors are regulated to cooperate with transcription factors, especially DNA/histone modifying-enzymes. It has been known that DNA/histone modifying-enzymes are regulated by post-translational modifications. And the most common and important modification is phosphorylation. Even though various DNA/histone modifying-enzymes have been classified and partly explained how phosphorylated sites of these enzymes function characteristically in recent studies. It still needs to find out the relationship between phosphorylation of these enzymes and the diseases-associated transcriptional regulation. Here this review describes how phosphorylation affects the transcription activity of these enzymes and other functions, including protein stability, subcellular localization, binding to chromatin, and interaction with other proteins.
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