Fig. 4

Levels of regulation of NKG2DL expression. Transcriptional level: 1) The transcription factors p53, E2F-1, HSF-1, and NF-κB promote the transcription of NKG2DL genes; 2) After acting on tumor cell membrane surface receptors, growth factors promote NKG2DL gene transcription through the PI3K/AKT pathway; 3) Expression of 2-HG due to IDH gene mutation can inhibit the transcription of the NKG2DL gene. Translational level: miRNA binding to NKG2DL mRNA affects its stability and decreases NKG2DL expression. Post-translational level: 1) ADAM and MMP hydrolyze the intracellular part of NKG2DL such that NKG2DL is secreted and the expression level is reduced; 2) The secretion of exosomes with NKG2DL can reduce the expression levels of NKG2DL and NKG2D receptor