Fig. 8: Graphical abstract.

The diagram illustrates the mechanism underlying EZH2-92aa-mediated immune escape of GSCs from NK cells. EZH-92aa, encoded by circEZH2 in GSCs, can not only directly bind to the promoters of MICA/B and represses their transcription, but also serves as a decoy of E3-ligase FBXW7 to protect EZH2 from degradation and indirectly impedes the expression of ULBPs. The downregulation of NKG2DLs (MICA/B and ULBPs) caused by EZH2-92aa is responsible for the immune evasion of GSCs from NK cytotoxicity.