Role of histone methyltransferase “EZH2” in human cancer

Abstract

Epigenetic alternations significantly contribute many disease progressions as the genetic changes do. However, there is a crucial difference between genetic and epigenetic alterations, which has important implications for development of cancer treatments. Therefore it is tough duty and also necessary to identify the all pathways or mechanism by which they work for the development of strategies to impede their abnormal behaviours.
Chromatin condensation or relaxation is closely linked with tumorigenesis or cancer by regulating the pattern of gene expression. Methylation is often associated with silencing of many genes. Polycomb group proteins are important for the somatic maintenance of imprinting and for maintaining the silenced state of homeotic genes. The frequent deregulation of PcG activities in human tumors has direct oncogenic effects and results essential for cancer cell proliferation. Ezh2, a Polycomb group protein is the catalytic subunit of PRC2 having conserved SET domain targets H3K27me3. There is little contribution of Ezh2 is known till this date, still H3K27me3 and DNA methylation play a role together in gene silencing by loss of tumor suppression. Ezh2 also linked to histone deacetylation and it is shown that HDAC which is associated to EED is required for PRC2 to perform its function.
Here we investigate the functional role of EZH2 in lymph node and gall bladder cancer progression. EZH2 and SUZ12 transcripts were consistently elevated in lymph node carcinoma as compared with normal blood cell. Band intensity analysis demonstrated that EZH2 and SUZ12 protein levels were strongly associated with lymph node cancer aggressiveness. HDAC overexpression in tis cancer supports the EZH2-mediated cell invasion required an intact SET domain and histone deacetylase activity. This study provides the functional link between H3K27me3, DNMTs and HDACs in cancer aggression.