Abstract
Epigenetic alterations, such as histone modification, DNA methylation, and miRNA-mediated processes, are critically associated with various mechanisms of proliferation and metastasis in several types of cancer. To overcome the side effects and limited effectiveness of drugs for cancer treatment, there is a continuous need for the identification of more effective drug targets and the execution of mechanism of action (MOA) studies. Recently, epigenetic modifiers have been recognized as important therapeutic targets for hepatocellular carcinoma (HCC) based on their reported abilities to suppress HCC metastasis and proliferation in both in vivo and in vitro studies. Therefore, here, we introduce epigenetic modifiers and alterations related to HCC metastasis and proliferation, and their molecular mechanisms in HCC metastasis. The existing data suggest that the study of epigenetic modifiers is important for the development of specific inhibitors and diagnostic targets for HCC treatment.
Highlights
Hepatocellular carcinoma (HCC), a common primary liver cancer, is the second leading cause of death in cancer patients, and is caused by chronic hepatitis B and C virus (HBV and HCV) infections and other factors, such as alcohol, diabetes, and aflatoxin exposure [1,2]
DNA methylation catalyzed by DNA methyltransferases (DNMTs) is a chemical modification of DNA that occurs by conjugation of a methyl group to the 5’ carbon position of the cytosine ring, which is crucial for regulating gene expression [50]
Another study on the role of hepatocyte growth factor (HGF) in HCC metastasis reported that the induction of DNMT1 expression by HGF resulted in DNA hypermethylation of tumor suppressor genes, including MYOCD, PANX2, and LHX9 [57]
Summary
Hepatocellular carcinoma (HCC), a common primary liver cancer, is the second leading cause of death in cancer patients, and is caused by chronic hepatitis B and C virus (HBV and HCV) infections and other factors, such as alcohol, diabetes, and aflatoxin exposure [1,2]. Several papers reported that various epigenetic modifiers and alterations (e.g., microRNA (miRNA), histone modification, and DNA methylation) participate in HCC proliferation and metastasis via epigenetic regulation of oncogenes and tumor suppressor genes, suggesting that epigenetic modifiers are important therapeutic targets for the development of specific inhibitors of HCC [5,6,7]. Abnormal regulation of miRNA expression is linked to tumor progression and metastasis [16,17]. In this miRNA section, we will discuss epithelial–mesenchymal transition (EMT)-related miRNAs in HCC and their oncogenic or tumor suppressive functions (Table 1)
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