Abstract |
MicroRNAs ( miRNAs) delivered by gastric cancer (GC)-secreted extracellular vesicles (GC-EVs) are associated with the immune escape in GC. Microarray analysis based on the GEO: GSE112369 dataset identified the presence of poorly expressed CXXC finger protein 4 (CXXC4) in GC, which was validated in clinical samples of GC patients. Moreover, prediction based on TargetScan analysis demonstrated the putative miR-675-3p binding site in the 3' UTR region of CXXC4. Thereby, our study aims to determine the role of GC-EV-encapsulated miR-675-3p in GC. First, CXXC4 was found to be negatively correlated with programmed cell death 1 ligand 1 (PD-L1). The effects of mitogen-activated protein kinase (MAPK) signaling on GC were evaluated using activator of the MAPK pathway. The overexpression of CXXC4 led to a downregulated MAPK signaling pathway, thus decreasing PD-L1 expression to augment the proliferation and activation of T cells co-cultured with GC HGC-27 cells. GC-EV-encapsulated miR-675-3p negatively regulated the expression of its target gene CXXC4. GC-EV-encapsulated miR-675-3p increased PD-L1 expression to stimulate the immune escape in vitro and EV-encapsulated miR-675-3p accelerated cisplatin resistance in vivo. Collectively, the aforementioned findings present a mechanism in which EV-mediated miR-675-3p upregulates PD-L1 expression, promoting immune escape in GC.
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Authors | Ping Li, Xingdong Luo, Yue Xie, Pengfei Li, Fangyong Hu, Junfeng Chu, Xiaojun Chen, Wenbo Song, Ali Wang, Guangyu Tian, Xiang Gu |
Journal | Molecular therapy. Nucleic acids
(Mol Ther Nucleic Acids)
Vol. 22
Pg. 615-626
(Dec 04 2020)
ISSN: 2162-2531 [Print] United States |
PMID | 33230461
(Publication Type: Journal Article)
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Copyright | © 2020 The Authors. |