Unveiling the hidden AP-1: revealing the crucial role of AP-1 in ccRCC at single-cell resolution
Abstract Clear cell renal cell carcinoma (ccRCC), as the most common histological subtype of kidney cancer, has been reported to originate primarily from proximal tubule (PT) cells in the kidney. However, the current research on its associated molecular mechanisms remains relatively limited. In our...
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-023-01913-9 |
| _version_ | 1797377151568183296 |
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| author | Jie Zheng Fengling Liu Cheng Su |
| author_facet | Jie Zheng Fengling Liu Cheng Su |
| author_sort | Jie Zheng |
| collection | DOAJ |
| description | Abstract Clear cell renal cell carcinoma (ccRCC), as the most common histological subtype of kidney cancer, has been reported to originate primarily from proximal tubule (PT) cells in the kidney. However, the current research on its associated molecular mechanisms remains relatively limited. In our study, we analyzed multiple single-cell multi-omics datasets obtained from various research teams, revealing the significant role of the activator protein 1 (AP-1) in ccRCC tumorigenesis. The motif activity analysis of transcription factors (TFs) showed a predominant activation of AP-1 in ccRCC cancer cells compared to PT cells. Furthermore, our findings at single-cell resolution revealed a notable absence of AP-1 expression in PT cells when compared to ccRCC cancer cells. In bulk-RNA of discovery cohort, no differential expression of AP-1 was detected in normal kidney and ccRCC samples, which may be attributed to confounding effects in bulk-RNA sequencing. Meanwhile, spatial transcriptomics analysis demonstrated a broader expression range of the AP-1 compared to the ccRCC marker CA9. Moreover, we observed chromatin accessibility of the AP-1 in various cell-types, including PT cells, suggesting that the transcriptional expression of AP-1 in PT cells may be influenced by subsequent transcriptional modifications, reflecting the complex regulatory mechanism of AP-1 transcription. These findings provide important insights for a deeper understanding of the function and regulatory mechanisms of AP-1 in ccRCC, thereby establishing a theoretical foundation for future clinical research and the development of treatment strategies. |
| first_indexed | 2024-03-08T19:49:36Z |
| format | Article |
| id | doaj.art-aeeefde6391044b7aa0754f419eb1fed |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-03-08T19:49:36Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-aeeefde6391044b7aa0754f419eb1fed2023-12-24T12:11:22ZengBMCMolecular Cancer1476-45982023-12-012211610.1186/s12943-023-01913-9Unveiling the hidden AP-1: revealing the crucial role of AP-1 in ccRCC at single-cell resolutionJie Zheng0Fengling Liu1Cheng Su2Department of Urology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Hematology, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Pediatric Surgery, The First Affiliated Hospital of Guangxi Medical UniversityAbstract Clear cell renal cell carcinoma (ccRCC), as the most common histological subtype of kidney cancer, has been reported to originate primarily from proximal tubule (PT) cells in the kidney. However, the current research on its associated molecular mechanisms remains relatively limited. In our study, we analyzed multiple single-cell multi-omics datasets obtained from various research teams, revealing the significant role of the activator protein 1 (AP-1) in ccRCC tumorigenesis. The motif activity analysis of transcription factors (TFs) showed a predominant activation of AP-1 in ccRCC cancer cells compared to PT cells. Furthermore, our findings at single-cell resolution revealed a notable absence of AP-1 expression in PT cells when compared to ccRCC cancer cells. In bulk-RNA of discovery cohort, no differential expression of AP-1 was detected in normal kidney and ccRCC samples, which may be attributed to confounding effects in bulk-RNA sequencing. Meanwhile, spatial transcriptomics analysis demonstrated a broader expression range of the AP-1 compared to the ccRCC marker CA9. Moreover, we observed chromatin accessibility of the AP-1 in various cell-types, including PT cells, suggesting that the transcriptional expression of AP-1 in PT cells may be influenced by subsequent transcriptional modifications, reflecting the complex regulatory mechanism of AP-1 transcription. These findings provide important insights for a deeper understanding of the function and regulatory mechanisms of AP-1 in ccRCC, thereby establishing a theoretical foundation for future clinical research and the development of treatment strategies.https://doi.org/10.1186/s12943-023-01913-9AP-1Clear cell renal cell carcinomascATACscRNASpatial transcriptomics |
| spellingShingle | Jie Zheng Fengling Liu Cheng Su Unveiling the hidden AP-1: revealing the crucial role of AP-1 in ccRCC at single-cell resolution Molecular Cancer AP-1 Clear cell renal cell carcinoma scATAC scRNA Spatial transcriptomics |
| title | Unveiling the hidden AP-1: revealing the crucial role of AP-1 in ccRCC at single-cell resolution |
| title_full | Unveiling the hidden AP-1: revealing the crucial role of AP-1 in ccRCC at single-cell resolution |
| title_fullStr | Unveiling the hidden AP-1: revealing the crucial role of AP-1 in ccRCC at single-cell resolution |
| title_full_unstemmed | Unveiling the hidden AP-1: revealing the crucial role of AP-1 in ccRCC at single-cell resolution |
| title_short | Unveiling the hidden AP-1: revealing the crucial role of AP-1 in ccRCC at single-cell resolution |
| title_sort | unveiling the hidden ap 1 revealing the crucial role of ap 1 in ccrcc at single cell resolution |
| topic | AP-1 Clear cell renal cell carcinoma scATAC scRNA Spatial transcriptomics |
| url | https://doi.org/10.1186/s12943-023-01913-9 |
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