miR-194-5p down-regulates tumor cell PD-L1 expression and promotes anti-tumor immunity in pancreatic cancer
| Autor: | Ying Chen, Lijuan Zhang, Ruijie Dong, Jieyou Zhang, Chao Gu, Guangze Yang, Rongxin Zhang, Jingyi Zhao, Xin Li, Chengzhi Wang, Xiangdong Guo, Qing Xi, Yan Li |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Immunology Datasets as Topic Down-Regulation CD8-Positive T-Lymphocytes B7-H1 Antigen 03 medical and health sciences Mice 0302 clinical medicine Immune system Pancreatic cancer PD-L1 Cell Line Tumor Tumor Microenvironment Immunology and Allergy Medicine Cytotoxic T cell Animals Humans Survival rate Pharmacology biology business.industry Cancer medicine.disease Gene Expression Regulation Neoplastic Pancreatic Neoplasms MicroRNAs 030104 developmental biology HEK293 Cells Tumor progression 030220 oncology & carcinogenesis Cancer research biology.protein Tumor Escape business CD8 |
| Zdroj: | International immunopharmacology. 97 |
| ISSN: | 1878-1705 |
| Popis: | Pancreatic cancer is a highly malignant cancer of the digestive tract. Studies have shown that in some types of cancer, a high level of microRNA-194-5p (miR-194-5p) is beneficial for controlling tumor progression, while in other cancers it plays a completely opposite role. However, how miR-194-5p affects anti-tumor immunity of pancreatic cancer remains unclear. In this study, we found that high expression of miR-194-5p in human pancreatic cancer patients is associated with a better survival rate, while increased expression of programmed cell death ligand 1 (PD-L1) in human pancreatic cancer patients is associated with a worse survival rate. In pancreatic cancer, the expression level of PD-L1 is negatively correlated with the expression level of miR-194-5p, and we identified that PD-L1 was target gene of miR-194-5p. In addition, we found that overexpression of miR-194-5p inhibited the migration, invasion and proliferation of pancreatic cancer cells in vitro. The orthotopic mouse model of pancreatic cancer shown that miR-194-5p suppressed the progression of pancreatic cancer, promoted the infiltration of CD8+ T cells in tumor immune microenvironments, and enhanced the IFN-γ production of CD8+ T cells. Consistently, the co-culture experiments showed that overexpression of miR-194-5p in tumor cell enhanced IFN-γ production by CD8+ T cells. In conclusion, miR-194-5p may serve as a novel immunotherapeutic target for pancreatic ductal adenocarcinoma (PDAC) by inhibiting the expression of PD-L1, and play important roles in inhibiting the progression of pancreatic cancer and boosting the anti-tumor effect of CD8+ T cells. |
| Databáze: | OpenAIRE |
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