PPARγ agonist inhibits c-Myc-mediated colorectal cancer tumor immune escape.

Liuqian Xu, Suning Che, Huiqing Chen, Qian Liu, Juanjuan Shi, Jianhua Jin, Yongzhong Hou

Journal of cellular biochemistry 2023 Aug

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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. © 2023 Wiley Periodicals LLC.

Citation

Liuqian Xu, Suning Che, Huiqing Chen, Qian Liu, Juanjuan Shi, Jianhua Jin, Yongzhong Hou. PPARγ agonist inhibits c-Myc-mediated colorectal cancer tumor immune escape. Journal of cellular biochemistry. 2023 Aug;124(8):1145-1154