Abstract
Nasopharyngeal carcinoma (NPC) is one of the most common tumors of head and neck in the Southeast Asia. PD-L1-dependent immune escape plays a critical role involved in NPC development. BPIFB1 has previously reported to take tumor-suppressive actions on NPC cell proliferation and migration. Nonetheless, the function of BPIFB1 in immune escape remains largely elusive. Expression pattern on mRNA and protein levels of target genes in NPC patients’ samples and cell lines were examined by qRT-PCR, western blot, and immunohistochemistry staining, respectively. The assessment of CD8+ T-cell apoptosis and expression was determined by flow cytometry. Molecular interactions were verified using chromatin immunoprecipitation (ChIP) and luciferase reporter assay. BPIFB1 was downregulated in NPC tumor tissues, exhibiting a negative correlation of PD-L1. Overexpression of BPIFB1 significantly inhibited the expression of PD-L1, suppressing the apoptosis and enhancing the expression of CD8+ T cells. Mechanistically, BPIFB1 was found to repress the expression of STAT1, which was identified to be an upstream activator of PD-L1. Furthermore, the EBV-encoded miR-BART4 overexpressed in NPC cells could directly target and inhibit BPIFB1. This study provided a comprehensive understanding of the molecular mechanism for the upstream and downstream pathway of BPIFB1 related with immune escape, indicating a novel approach for the treatment of NPC.
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We would like to give our sincere gratitude to the reviewers for their constructive comments.
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This work was supported by the Project of Changsha Natural Science Foundation (No. kq2202023).
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Conception and design of study: Guoqun Chen. Acquisition of data: Jiaodi Cai; Li **ao; Dan Wang; and Zhiming Liao. Analysis and interpretation of data: Jiao Liu and Yadong Zhou. Drafting the manuscript: Jiaodi Cai. Revising the manuscript critically for important intellectual content: Guoqun Chen. All authors read and approved the final manuscript.
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Cai, J., **ao, L., Liu, J. et al. BPIFB1, Serving as a Downstream Effector of EBV-miR-BART4, Blocks Immune Escape of Nasopharyngeal Carcinoma via Inhibiting PD-L1 Expression. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10719-3
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DOI: https://doi.org/10.1007/s10528-024-10719-3