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01-03-2017 | Original Article

A polymorphism in the promoter region of PD-L1 serves as a binding-site for SP1 and is associated with PD-L1 overexpression and increased occurrence of gastric cancer

Authors: Li-Hua Tao, Xin-Ru Zhou, Fu-Chao Li, Qi Chen, Fan-Yi Meng, Yong Mao, Rui Li, Dong Hua, Hong-Jian Zhang, Wei-Peng Wang, Wei-Chang Chen

Published in: Cancer Immunology, Immunotherapy | Issue 3/2017

Abstract

PD-L1 is a member of the B7 family co-inhibitory molecules and plays a critical role in tumor immune escape. In this study, we found a polymorphism rs10815225 in the PD-L1 promoter region was significantly associated with the occurrence of gastric cancer. The GG homozygous frequency was higher in the cancer patients than that in the precancerous lesions, which was higher than that in the health controls. This polymorphism locates in the binding-site of Sp1 transcription factor (SP1). The expression level of PD-L1 mRNA in the GG homozygous cancer patients was apparently higher than that in the GC heterozygotes. Luciferase reporter results showed that SP1 bonded to rs10815225 G-allelic PD-L1 promoter instead of C-allelic. Upregulation and knockdown of SP1 resulted in elevation and attenuation of PD-L1 in SGC-7901 cells, respectively. The chromatin immunoprecipitation results further confirmed the binding of SP1 to the promoter of PD-L1. Additionally, rs10815225 was found to be in disequilibrium with a functional polymorphism rs4143815 in the PD-L1 3′-UTR, and the haplotypes of these two polymorphisms were also markedly related to gastric cancer risk. These results revealed a novel mechanism underlying genetic polymorphisms influencing PD-L1 expression modify gastric cancer susceptibility.

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Title: A polymorphism in the promoter region of PD-L1 serves as a binding-site for SP1 and is associated with PD-L1 overexpression and increased occurrence of gastric cancer
Authors: Li-Hua Tao
Xin-Ru Zhou
Fu-Chao Li
Qi Chen
Fan-Yi Meng
Yong Mao
Rui Li
Dong Hua
Hong-Jian Zhang
Wei-Peng Wang
Wei-Chang Chen
Publication date: 01-03-2017
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 3/2017
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-016-1936-0

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