PPARγ agonist inhibits c‐Myc‐mediated colorectal cancer tumor immune escape

Abstract As a master transcription factor, c‐Myc plays an important role in promoting tumor immune escape. In addition, PPARγ (peroxisome proliferator‐activated receptor γ) regulates cell metabolism, inflammation, and tumor progression, while the effect of PPARγ on c‐Myc‐mediated tumor immune escape is still unclear. Here we found that cells treated with PPARγ agonist pioglitazone (PIOG) reduced c‐Myc protein expression in a PPARγ‐dependent manner. qPCR analysis showed that PIOG had no significant effect on c‐Myc gene levels. Further analysis showed that PIOG decreased c‐Myc protein half‐life. Moreover, PIOG increased the binding of c‐Myc to PPARγ, and induced c‐Myc ubiquitination and degradation. Importantly, c‐Myc increased PD‐L1 and CD47 immune checkpoint protein expression and promoted tumor immune escape, while PIOG inhibited this event. These findings suggest that PPARγ agonist inhibited c‐Myc‐mediated tumor immune escape by inducing its ubiquitination and degradation.