Epigenetic Changes Affecting the Development of Hepatocellular Carcinoma

Abstract

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.

Identification of Novel Biomarkers in Peripheral Blood Mononuclear Cells of Hepatocellular Carcinoma Patients

“…Methylation mainly affects the Cytosine base (C) when it is followed by a Guanine (G), the so-called CpG sites. In human DNA, 70-80% of CpG sites are methylated [26].…”

Epigenetics of alcohol-related liver diseases

“…[145]The role of environmental factorsincluding alcohol consumption, and the epigenetic changes that promote the development of HCC have been studied extensively. [42,146,147] The role of epidrugs in the management of liver disease is most established in the field of HCC. This topic has been reviewed recently by Fernandez-Barrena et al [28] The field of epidrugs for the treatment of ARLD and NAFLD is not as developed as that for HCC.…”

Liver-specific deletion of miR-181ab1 reduces liver tumour progression via upregulation of CBX7

“…Amongst the numerous molecular alterations in HCCs, it is increasingly recognised that microRNAs and epigenetic modifiers play important roles in hepatocarcinogenesis [ 2 , 8 – 11 ]. However, their regulatory circuits are very complex [ 12 ], and it is crucial to unravel their regulation to fully explore their impact on liver cancer, including its potential treatment in vivo [ 2 , 6 , 9 , 10 , 13 – 15 ]. We and others have shown miR-181a induced hepatocyte epithelial–mesenchymal transition (EMT) and was up-regulated in human cirrhosis and HCC [ 16 – 19 ].…”