| Autor: |
You-Zhe Lin, Shu-Hsuan Liu, Wan-Rong Wu, Yi-Chun Shen, Yuan-Liang Wang, Chien-Ching Liao, Pei-Le Lin, Han Chang, Liang-Chih Liu, Wei-Chung Cheng, Shao-Chun Wang |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Computational and Structural Biotechnology Journal, Vol 20, Iss , Pp 241-251 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2001-0370 |
| DOI: |
10.1016/j.csbj.2021.12.020 |
| Popis: |
Programmed cell death protein 1 (PD-1)/ programmed cell death protein ligand 1 (PD-L1) is the key immune checkpoint governing evasion of advanced cancer from immune surveillance. Immuno-oncology (IO) therapy targeting PD-1/PD-L1 with traditional antibodies is a promising approach to multiple cancer types but to which the response rate remains moderate in breast cancer, calling for the need of exploring alternative IO targeting approaches. A miRNA-gene network was integrated by a bioinformatics approach and corroborated with The Cancer Genome Atlas (TCGA) to screen miRNAs regulating immune checkpoint genes and associated with patient survival. Here we show the identification of a novel microRNA miR-4759 which repressed RNA expression of the PD-L1 gene. miR-4759 targeted the PD-L1 gene through two binding motifs in the 3′ untranslated region (3′-UTR) of PD-L1. Reconstitution of miR-4759 inhibited PD-L1 expression and sensitized breast cancer cells to killing by immune cells. Treatment with miR-4759 suppressed tumor growth of orthotopic xenografts and promoted tumor infiltration of CD8+ T lymphocytes in immunocompetent mice. In contrast, miR-4759 had no effect to tumor growth in immunodeficient mice. In patients with breast cancer, expression of miR-4759 was preferentially downregulated in tumors compared to normal tissues and was associated with poor overall survival. Together, our results demonstrated miR-4759 as a novel non-coding RNA which promotes anti-tumor immunity of breast cancer. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
