Histone methylation and methyltransferase enzyme Set8 in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide. The epigenetic modifications, which are involved in virtually all cellular processes are also involved in the carcinogenic process, and this is a growing new field of investigation. HCC has also been associated with several epigenetic aberrations which include the ones in histone modifications, histone methyltransferase enzymes, and the epigenetic machinery. The transition from cirrhosis to HCC is related to senescence bypass, and the distinctions between senescence and immortality in HCC cell lines. Global levels of H3K4me3, H3K9me3, H3K27me3, H3K36me3, H3R2me2, H3R17me2 and H4K20me3 histone marks were evaluated in well-differentiated and poorly differentiated HCC cell lines in the presence and absence of TGF-β induced senescence. No prominent changes in the levels of these histone modifications were indentified in response to TGF-β induced senescence. However, H4K20me3 levels appeared to correlate with the differentiation status of the cell lines, where a loss of methylation was observed in poorly differentiated cell lines. In order to address the mechanism of this loss, H4K20 specific methyltransferases were analyzed in terms of their transcript levels, and only the expression pattern of monomethyl transferase Set8 was found to correlate with the H4K20me3 methylation patterns. A potential role played by Set8 in HCC development was investigated via overexpression and knockdown studies. But no significant role could be attributed to this enzyme in this study.