Hepatocellular carcinoma (HCC) development is characterized by the presence of epigenetic alterations, including promoter
DNA hypermethylation and post-translational modifications of
histone, which profoundly affect expression of a wide repertoire of genes critical for
cancer development. Emerging data suggest that deregulation of polycomb group (PcG)
proteins, which are key
chromatin modifiers repressing gene transcription during developmental stage, plays a causative role in
oncogenesis. PcG
proteins assemble into
polycomb repressive complex 1 (PRC1) and
polycomb repressive complex 2 (PRC2) to impose the
histone H3 lysine 27 trimethylation (H3K27me3) modification for repression. In this review, we will first recapitulate the mechanisms of two key epigenetic pathways: DNA methylation and histone modifications. Specifically, we will focus our discussion on the molecular roles of PcG
proteins. Next, we will highlight recent findings on PcG
proteins, their clinicopathological implication and their downstream molecular consequence in hepatocarcinogenesis. Last but not least, we will consider the therapeutic potential of targeting
enhancer of zeste homolog 2 (EZH2) as a possible treatment for HCC. Improving our understanding on the roles of PcG
proteins in hepatocarcinogenesis can benefit the development of epigenetic-based
therapy.