Multi-omics analysis for potential inflammation-related genes involved in tumour immune evasion via extended application of epigenetic data
Accumulating evidence suggests that inflammation-related genes may play key roles in tumour immune evasion. Programmed cell death ligand 1 (PD-L1) is an important immune checkpoint involved in mediating anti-tumour immunity. We performed multi-omics analysis to explore key inflammation-related genes...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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The Royal Society
2022-08-01
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| Series: | Open Biology |
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsob.210375 |
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| author | Chenshen Huang Ning Wang Na Zhang Zhizhong Chen Zhizhan Ni Xiaohong Liu Hao Xiong Huahao Xie Boxu Lin Bujun Ge Qi Huang Bing Du |
| author_facet | Chenshen Huang Ning Wang Na Zhang Zhizhong Chen Zhizhan Ni Xiaohong Liu Hao Xiong Huahao Xie Boxu Lin Bujun Ge Qi Huang Bing Du |
| author_sort | Chenshen Huang |
| collection | DOAJ |
| description | Accumulating evidence suggests that inflammation-related genes may play key roles in tumour immune evasion. Programmed cell death ligand 1 (PD-L1) is an important immune checkpoint involved in mediating anti-tumour immunity. We performed multi-omics analysis to explore key inflammation-related genes affecting the transcriptional regulation of PD-L1 expression. The open chromatin region of the PD-L1 promoter was mapped using the assay for transposase-accessible chromatin using sequencing (ATAC-seq) profiles. Correlation analysis of epigenetic data (ATAC-seq) and transcriptome data (RNA-seq) were performed to identify inflammation-related transcription factors (TFs) whose expression levels were correlated with the chromatin accessibility of the PD-L1 promoter. Chromatin immunoprecipitation sequencing (ChIP-seq) profiles were used to confirm the physical binding of the TF STAT2 and the predicted binding regions. We also confirmed the results of the bioinformatics analysis with cell experiments. We identified chr9 : 5449463–5449962 and chr9 : 5450250–5450749 as reproducible open chromatin regions in the PD-L1 promoter. Moreover, we observed a correlation between STAT2 expression and the accessibility of the aforementioned regions. Furthermore, we confirmed its physical binding through ChIP-seq profiles and demonstrated the regulation of PD-L1 by STAT2 overexpression in vitro. Multiple databases were also used for the validation of the results. Our study identified STAT2 as a direct upstream TF regulating PD-L1 expression. The interaction of STAT2 and PD-L1 might be associated with tumour immune evasion in cancers, suggesting the potential value for tumour treatment. |
| first_indexed | 2024-04-09T16:12:05Z |
| format | Article |
| id | doaj.art-3d683fec8513440baf8152adff1ebcfd |
| institution | Directory Open Access Journal |
| issn | 2046-2441 |
| language | English |
| last_indexed | 2024-04-09T16:12:05Z |
| publishDate | 2022-08-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj.art-3d683fec8513440baf8152adff1ebcfd2023-04-24T09:16:43ZengThe Royal SocietyOpen Biology2046-24412022-08-0112810.1098/rsob.210375Multi-omics analysis for potential inflammation-related genes involved in tumour immune evasion via extended application of epigenetic dataChenshen Huang0Ning Wang1Na Zhang2Zhizhong Chen3Zhizhan Ni4Xiaohong Liu5Hao Xiong6Huahao Xie7Boxu Lin8Bujun Ge9Qi Huang10Bing Du11Department of Gastrointestinal Surgery, Fujian Provincial Hospital, Fuzhou, People's Republic of ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, People's Republic of ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, People's Republic of ChinaShengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People's Republic of ChinaDepartment of General Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, People's Republic of ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, People's Republic of ChinaDepartment of General Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, People's Republic of ChinaDepartment of General Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of ChinaDepartment of General Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, People's Republic of ChinaAccumulating evidence suggests that inflammation-related genes may play key roles in tumour immune evasion. Programmed cell death ligand 1 (PD-L1) is an important immune checkpoint involved in mediating anti-tumour immunity. We performed multi-omics analysis to explore key inflammation-related genes affecting the transcriptional regulation of PD-L1 expression. The open chromatin region of the PD-L1 promoter was mapped using the assay for transposase-accessible chromatin using sequencing (ATAC-seq) profiles. Correlation analysis of epigenetic data (ATAC-seq) and transcriptome data (RNA-seq) were performed to identify inflammation-related transcription factors (TFs) whose expression levels were correlated with the chromatin accessibility of the PD-L1 promoter. Chromatin immunoprecipitation sequencing (ChIP-seq) profiles were used to confirm the physical binding of the TF STAT2 and the predicted binding regions. We also confirmed the results of the bioinformatics analysis with cell experiments. We identified chr9 : 5449463–5449962 and chr9 : 5450250–5450749 as reproducible open chromatin regions in the PD-L1 promoter. Moreover, we observed a correlation between STAT2 expression and the accessibility of the aforementioned regions. Furthermore, we confirmed its physical binding through ChIP-seq profiles and demonstrated the regulation of PD-L1 by STAT2 overexpression in vitro. Multiple databases were also used for the validation of the results. Our study identified STAT2 as a direct upstream TF regulating PD-L1 expression. The interaction of STAT2 and PD-L1 might be associated with tumour immune evasion in cancers, suggesting the potential value for tumour treatment.https://royalsocietypublishing.org/doi/10.1098/rsob.210375STAT2PD-L1immune evasionATAC-seqimmune checkpoint therapyepigenetics |
| spellingShingle | Chenshen Huang Ning Wang Na Zhang Zhizhong Chen Zhizhan Ni Xiaohong Liu Hao Xiong Huahao Xie Boxu Lin Bujun Ge Qi Huang Bing Du Multi-omics analysis for potential inflammation-related genes involved in tumour immune evasion via extended application of epigenetic data Open Biology STAT2 PD-L1 immune evasion ATAC-seq immune checkpoint therapy epigenetics |
| title | Multi-omics analysis for potential inflammation-related genes involved in tumour immune evasion via extended application of epigenetic data |
| title_full | Multi-omics analysis for potential inflammation-related genes involved in tumour immune evasion via extended application of epigenetic data |
| title_fullStr | Multi-omics analysis for potential inflammation-related genes involved in tumour immune evasion via extended application of epigenetic data |
| title_full_unstemmed | Multi-omics analysis for potential inflammation-related genes involved in tumour immune evasion via extended application of epigenetic data |
| title_short | Multi-omics analysis for potential inflammation-related genes involved in tumour immune evasion via extended application of epigenetic data |
| title_sort | multi omics analysis for potential inflammation related genes involved in tumour immune evasion via extended application of epigenetic data |
| topic | STAT2 PD-L1 immune evasion ATAC-seq immune checkpoint therapy epigenetics |
| url | https://royalsocietypublishing.org/doi/10.1098/rsob.210375 |
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