Exploring RPA1-ETAA1 axis via high-throughput data analysis: implications for PD-L1 nuclear translocation and tumor-immune dynamics in liver cancer
IntroductionETAA1 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 & resultsOur findings associate Programmed Death- Ligand1 (PD-L1) with the RPA1-ETAA1 axis, suggesting...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-11-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1492531/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850160460487196672 |
|---|---|
| author | Gaofeng Qin Gaofeng Qin Zengkuan Chen Zengkuan Chen Weihong Tian Hongbo Chen Yu Zhang Yu Zhang Wangzhi Wei Wangzhi Wei |
| author_facet | Gaofeng Qin Gaofeng Qin Zengkuan Chen Zengkuan Chen Weihong Tian Hongbo Chen Yu Zhang Yu Zhang Wangzhi Wei Wangzhi Wei |
| author_sort | Gaofeng Qin |
| collection | DOAJ |
| description | IntroductionETAA1 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 & resultsOur 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 & conclusionThese findings expand the role of the RPA1-ETAA1 axis beyond DNA repair, highlighting its potential as a target for cancer therapy. |
| format | Article |
| id | doaj-art-ff0bf2aef5d24c68a91d99b114d92ea9 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-ff0bf2aef5d24c68a91d99b114d92ea92025-08-20T02:23:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-11-011510.3389/fimmu.2024.14925311492531Exploring RPA1-ETAA1 axis via high-throughput data analysis: implications for PD-L1 nuclear translocation and tumor-immune dynamics in liver cancerGaofeng Qin0Gaofeng Qin1Zengkuan Chen2Zengkuan Chen3Weihong Tian4Hongbo Chen5Yu Zhang6Yu Zhang7Wangzhi Wei8Wangzhi Wei9Liaoning 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, ChinaCollege of Basic Medical Science, Jinzhou Medical University, Jinzhou, Liaoning, ChinaLiaoning 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, ChinaCollege of Basic Medical Science, Jinzhou Medical University, Jinzhou, Liaoning, ChinaLiaoning 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, ChinaDepartment of Intensive Care Medicine, Yingkou Central Hospital, Yingkou, Liaoning, ChinaLiaoning 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, ChinaCollege of Basic Medical Science, Jinzhou Medical University, Jinzhou, Liaoning, ChinaLiaoning 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, ChinaCollege of Basic Medical Science, Jinzhou Medical University, Jinzhou, Liaoning, ChinaIntroductionETAA1 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 & resultsOur 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 & conclusionThese findings expand the role of the RPA1-ETAA1 axis beyond DNA repair, highlighting its potential as a target for cancer therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1492531/fullreplication protein A (RPA)Ewing tumor-associated antigen 1 (ETAA1)PD-L1immune infiltrationliver cancer |
| spellingShingle | Gaofeng Qin Gaofeng Qin Zengkuan Chen Zengkuan Chen Weihong Tian Hongbo Chen Yu Zhang Yu Zhang Wangzhi Wei Wangzhi Wei Exploring RPA1-ETAA1 axis via high-throughput data analysis: implications for PD-L1 nuclear translocation and tumor-immune dynamics in liver cancer Frontiers in Immunology replication protein A (RPA) Ewing tumor-associated antigen 1 (ETAA1) PD-L1 immune infiltration liver cancer |
| title | Exploring RPA1-ETAA1 axis via high-throughput data analysis: implications for PD-L1 nuclear translocation and tumor-immune dynamics in liver cancer |
| title_full | Exploring RPA1-ETAA1 axis via high-throughput data analysis: implications for PD-L1 nuclear translocation and tumor-immune dynamics in liver cancer |
| title_fullStr | Exploring RPA1-ETAA1 axis via high-throughput data analysis: implications for PD-L1 nuclear translocation and tumor-immune dynamics in liver cancer |
| title_full_unstemmed | Exploring RPA1-ETAA1 axis via high-throughput data analysis: implications for PD-L1 nuclear translocation and tumor-immune dynamics in liver cancer |
| title_short | Exploring RPA1-ETAA1 axis via high-throughput data analysis: implications for PD-L1 nuclear translocation and tumor-immune dynamics in liver cancer |
| title_sort | exploring rpa1 etaa1 axis via high throughput data analysis implications for pd l1 nuclear translocation and tumor immune dynamics in liver cancer |
| topic | replication protein A (RPA) Ewing tumor-associated antigen 1 (ETAA1) PD-L1 immune infiltration liver cancer |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1492531/full |
| work_keys_str_mv | AT gaofengqin exploringrpa1etaa1axisviahighthroughputdataanalysisimplicationsforpdl1nucleartranslocationandtumorimmunedynamicsinlivercancer AT gaofengqin exploringrpa1etaa1axisviahighthroughputdataanalysisimplicationsforpdl1nucleartranslocationandtumorimmunedynamicsinlivercancer AT zengkuanchen exploringrpa1etaa1axisviahighthroughputdataanalysisimplicationsforpdl1nucleartranslocationandtumorimmunedynamicsinlivercancer AT zengkuanchen exploringrpa1etaa1axisviahighthroughputdataanalysisimplicationsforpdl1nucleartranslocationandtumorimmunedynamicsinlivercancer AT weihongtian exploringrpa1etaa1axisviahighthroughputdataanalysisimplicationsforpdl1nucleartranslocationandtumorimmunedynamicsinlivercancer AT hongbochen exploringrpa1etaa1axisviahighthroughputdataanalysisimplicationsforpdl1nucleartranslocationandtumorimmunedynamicsinlivercancer AT yuzhang exploringrpa1etaa1axisviahighthroughputdataanalysisimplicationsforpdl1nucleartranslocationandtumorimmunedynamicsinlivercancer AT yuzhang exploringrpa1etaa1axisviahighthroughputdataanalysisimplicationsforpdl1nucleartranslocationandtumorimmunedynamicsinlivercancer AT wangzhiwei exploringrpa1etaa1axisviahighthroughputdataanalysisimplicationsforpdl1nucleartranslocationandtumorimmunedynamicsinlivercancer AT wangzhiwei exploringrpa1etaa1axisviahighthroughputdataanalysisimplicationsforpdl1nucleartranslocationandtumorimmunedynamicsinlivercancer |