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Inhibition of Yes-Associated Protein Down-Regulates PD-L1 (CD274) Expression in Human Malignant Pleural Mesothelioma

Inhibition of Yes-Associated Protein Down-Regulates PD-L1 (CD274) Expression in Human Malignant Pleural Mesothelioma

Ping-Chih Hsu, Jinbai Miao, Yu-Cheng Wang, Wen-Qian Zhang, Yi-Lin Yang, Chih-Wei Wang, Cheng-Ta Yang, Zhen Huang, Joanna You, Zhidong Xu, David M Jablons, Liang You

J Cell Mol Med. 2018 Jun;22(6):3139-3148.

PMID: 29575535

Abstract:

Although tumour PD-L1 (CD274) expression had been used as a predictive biomarker in checkpoint immunotherapy targeting the PD1/PD-L1 axis in various cancers, the regulation of PD-L1 (CD274) expression is unclear. Yes-associated protein (YAP), an important oncogenic protein in Hippo signalling pathway, reportedly promotes cancer development. We investigated whether inhibition of YAP down-regulates PD-L1 (CD274) in human malignant pleural mesothelioma (MPM). Western blotting showed that 2 human MPM cell lines (H2052 and 211H) had increased PD-L1 protein expression compared to H290, MS-1 and H28 cells. In H2052 and 211H cells, PD-L1 mRNA expression was significantly increased compared to other MPM cell lines; YAP knockdown by small interfering RNA decreased PD-L1 protein and mRNA expression. Forced overexpression of the YAP gene increased PD-L1 protein expression in H2452 cells. Chromatin immunoprecipitation (ChIP) assay showed the precipitation of PD-L1 enhancer region encompassing 2 putative YAP-TEAD-binding sites in H2052 cells. We found that, in human MPM tissue microarray samples, YAP and PD-L1 concurrently expressed in immunohistochemistry stain (n = 70, P < .05, chi-square). We conclude that PD-L1 is correlated with YAP expression, and inhibition of YAP down-regulates PD-L1 expression in human MPM. Further study of how YAP regulates PD-L1 in MPM is warranted.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248418	CD274 human			Price

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