Abstract
Simple SummaryHepatocellular carcinoma is a life-threatening disease. Despite many efforts to understand the exact pathogenesis and the signaling pathways involved in its formation, treatment remains unsatisfactory. Currently, an important function in the development of neoplastic diseases and treatment effects is attributed to changes taking place at the epigenetic level. Epigenetic studies revealed modified methylation patterns in HCC, dysfunction of enzymes engaged in the DNA methylation process, the aberrant function of non-coding RNAs, and a set of histone modifications that influence gene expression. The aim of this review is to summarize the current knowledge on the role of epigenetics in the formation of hepatocellular carcinoma.Hepatocellular carcinoma (HCC) remains a serious oncologic issue with still a dismal prognosis. So far, no key molecular mechanism that underlies its pathogenesis has been identified. Recently, by specific molecular approaches, many genetic and epigenetic changes arising during HCC pathogenesis were detected. Epigenetic studies revealed modified methylation patterns in HCC tumors, dysfunction of enzymes engaged in the DNA methylation process, and a set of histone modifications that influence gene expression. HCC cells are also influenced by the disrupted function of non-coding RNAs, such as micro RNAs and long non-coding RNAs. Moreover, a role of liver cancer stem cells in HCC development is becoming evident. The reversibility of epigenetic changes offers the possibility of influencing them and regulating their undesirable effects. All these data can be used not only to identify new therapeutic targets but also to predict treatment response. This review focuses on epigenetic changes in hepatocellular carcinoma and their possible implications in HCC therapy.
Highlights
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide [1]
We summarize the most crucial dysfunctions of signaling pathways and factors that lead to and facilitate the development of this most common primary liver cancer
The reaction of transferring a methyl moiety to the 5-carbon of cytosine is catalyzed by a class of DNA methyltransferases (Dnmts), of which mainly three enzymes play a role in cancer development and progression: Dnmt1, Dnmt3A, and Dnmt3B
Summary
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide [1]. It represents the most common form of liver cancer, responsible for over 90% of primary liver cancers. Current treatment options, such as hepatic resection, radiofrequency ablation, chemoembolization, or liver transplantation, are relatively effective in the early stages of HCC, when patients retain liver functional reserve. Many patients are diagnosed at a late stage and, are not eligible for such a treatment. The average survival rate of the treated patient is approximately two years [2]
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