EZH2 and hepatocellular carcinoma: For instance, IDH-mutation mediated DNA hypermethylation and EZH2-catalyzed H3K27 methylation transcriptionally suppress the expression of NK group 2D (NKG2D) ligands (e.g., ULBP1 and ULBP3) in glioma and hepatocellular carcinoma, respectively.369,370 Furthermore, circular EZH2 RNA derived from circularization of exon-2 and -3 of the EZH2 gene encodes a functional shortened version protein called EZH2-92aa which represses the transcription of multiple NKG2D ligands both directly (by binding to the gene promoters) and indirectly (by stabilizing EZH2).371