Exploring RPA1-ETAA1 axis via high-throughput data analysis: implications for PD-L1 nuclear translocation and tumor-immune dynamics in liver cancer.

Autor:	Qin G; Liaoning Technology and Engineering Center for Tumor Immunology and Molecular Theranotics, Collaborative Innovation Center for Age-related Disease, Life Science Institute, Jinzhou Medical University, Jinzhou, Liaoning, China.; College of Basic Medical Science, Jinzhou Medical University, Jinzhou, Liaoning, China., Chen Z; Liaoning Technology and Engineering Center for Tumor Immunology and Molecular Theranotics, Collaborative Innovation Center for Age-related Disease, Life Science Institute, Jinzhou Medical University, Jinzhou, Liaoning, China.; College of Basic Medical Science, Jinzhou Medical University, Jinzhou, Liaoning, China., Tian W; Liaoning Technology and Engineering Center for Tumor Immunology and Molecular Theranotics, Collaborative Innovation Center for Age-related Disease, Life Science Institute, Jinzhou Medical University, Jinzhou, Liaoning, China., Chen H; Department of Intensive Care Medicine, Yingkou Central Hospital, Yingkou, Liaoning, China., Zhang Y; Liaoning Technology and Engineering Center for Tumor Immunology and Molecular Theranotics, Collaborative Innovation Center for Age-related Disease, Life Science Institute, Jinzhou Medical University, Jinzhou, Liaoning, China.; College of Basic Medical Science, Jinzhou Medical University, Jinzhou, Liaoning, China., Wei W; Liaoning Technology and Engineering Center for Tumor Immunology and Molecular Theranotics, Collaborative Innovation Center for Age-related Disease, Life Science Institute, Jinzhou Medical University, Jinzhou, Liaoning, China.; College of Basic Medical Science, Jinzhou Medical University, Jinzhou, Liaoning, China.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Nov 26; Vol. 15, pp. 1492531. Date of Electronic Publication: 2024 Nov 26 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1492531
Abstrakt:	Introduction: ETAA1 is recruited to DNA damage sites via its RPA -binding and ATR -activating domain (AAD) motifs, where RPA binding is crucial for ETAA1's regulation of ATR activity. Methods & Results: Our findings associate Programmed Death- Ligand1 (PD-L1) with the RPA1-ETAA1 axis, suggesting that upregulated RPA1 -dependent ETAA1 may facilitate PD-L1 nuclear accumulation. We observed strong correlations between ETAA1 and RPA1 with the components involved in HDAC2-mediated deacetylation, clathrin -dependent endocytosis, and PD-L1 nucleocytoplasmic shuttling, aligning with the established regulatory pathway of PD-L1 nuclear translocation. Moreover, nuclear PD-L1 transactivates a panel of pro-inflammatory and immune response transcription factors, potentially reshaping the tumor immune microenvironment. We identified a landscape of infiltrating lymphocytes influenced by ETAA1, finding that levels of ETAA1 were negatively correlated with CD8 + T and Natural Killer T (NKT) cells, but positively correlated with CD4 + T helper 2 (Th2) cells, cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), neutrophils and regulatory T cells (Tregs), suggesting a potential role in immune evasion. Further analysis shows that the RPA1-ETAA1 axis is significantly associated with multiple metastasis mediators and unfavorable liver cancer progression, with higher expression observed in advanced stages and poorly differentiated subgroups. Discussion & Conclusion: These findings expand the role of the RPA1-ETAA1 axis beyond DNA repair, highlighting its potential as a target for cancer therapy. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Qin, Chen, Tian, Chen, Zhang and Wei.)
Databáze:	MEDLINE
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