Deciphering STAT3’s negative regulation of LHPP in ESCC progression through single-cell transcriptomics analysis
Abstract Background Esophageal Squamous Cell Carcinoma (ESCC) remains a predominant health concern in the world, characterized by high prevalence and mortality rates. Advances in single-cell transcriptomics have revolutionized cancer research by enabling a precise dissection of cellular and molecula...
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BMC
2024-10-01
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| Online Access: | https://doi.org/10.1186/s10020-024-00962-0 |
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| author | Yurao Chen Zemao Zheng Luoshai Wang Ronghuai Chen Ming He Xiang Zhao Liyan Jin Juan Yao |
| author_facet | Yurao Chen Zemao Zheng Luoshai Wang Ronghuai Chen Ming He Xiang Zhao Liyan Jin Juan Yao |
| author_sort | Yurao Chen |
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| description | Abstract Background Esophageal Squamous Cell Carcinoma (ESCC) remains a predominant health concern in the world, characterized by high prevalence and mortality rates. Advances in single-cell transcriptomics have revolutionized cancer research by enabling a precise dissection of cellular and molecular diversity within tumors. Objective This study aims to elucidate the cellular dynamics and molecular mechanisms in ESCC, focusing on the transcriptional influence of STAT3 (Signal Transducer and Activator of Transcription 3) and its interaction with LHPP, thereby uncovering potential therapeutic targets. Methods Single-cell RNA sequencing was employed to analyze 44,206 cells from tumor and adjacent normal tissues of ESCC patients, identifying distinct cell types and their transcriptional shifts. We conducted differential gene expression analysis to assess changes within the tumor microenvironment (TME). Validation of key regulatory interactions was performed using qPCR in a cohort of 21 ESCC patients and further substantiated through experimental assays in ESCC cell lines. Results The study revealed critical alterations in cell composition and gene expression across identified cell populations, with a notable shift towards pro-tumorigenic states. A significant regulatory influence of STAT3 on LHPP was discovered, establishing a novel aspect of ESCC pathogenesis. Elevated levels of STAT3 and suppressed LHPP expression were validated in clinical samples. Functional assays confirmed that STAT3 directly represses LHPP at the promoter level, and disruption of this interaction by promoter mutations diminished STAT3's repressive effect. Conclusion This investigation underscores the central role of STAT3 as a regulator in ESCC, directly impacting LHPP expression and suggesting a regulatory loop crucial for tumor behavior. The insights gained from our comprehensive cellular and molecular analysis offer a deeper understanding of the dynamics within the ESCC microenvironment. These findings pave the way for targeted therapeutic interventions focusing on the STAT3-LHPP axis, providing a strategic approach to improve ESCC management and prognosis. |
| format | Article |
| id | doaj-art-a3911e18c4ba43239ca32aa69894d971 |
| institution | OA Journals |
| issn | 1528-3658 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-a3911e18c4ba43239ca32aa69894d9712025-08-20T02:18:35ZengBMCMolecular Medicine1528-36582024-10-0130111510.1186/s10020-024-00962-0Deciphering STAT3’s negative regulation of LHPP in ESCC progression through single-cell transcriptomics analysisYurao Chen0Zemao Zheng1Luoshai Wang2Ronghuai Chen3Ming He4Xiang Zhao5Liyan Jin6Juan Yao7Department of Radiation Oncology, Huaian Hospital of Huaian CityDepartment of Radiation Oncology, Huaian Hospital of Huaian CityDepartment of Thoracic Surgery, Huaian Hospital of Huaian CityDepartment of Radiation Oncology, Huaian Hospital of Huaian CityDepartment of Radiation Oncology, Huaian Hospital of Huaian CityDepartment of Radiation Oncology, Huaian Hospital of Huaian CityDepartment of Oncology, Wujin Hospital Affiliated with Jiangsu UniversityDepartment of Radiation Oncology, Huaian Hospital of Huaian CityAbstract Background Esophageal Squamous Cell Carcinoma (ESCC) remains a predominant health concern in the world, characterized by high prevalence and mortality rates. Advances in single-cell transcriptomics have revolutionized cancer research by enabling a precise dissection of cellular and molecular diversity within tumors. Objective This study aims to elucidate the cellular dynamics and molecular mechanisms in ESCC, focusing on the transcriptional influence of STAT3 (Signal Transducer and Activator of Transcription 3) and its interaction with LHPP, thereby uncovering potential therapeutic targets. Methods Single-cell RNA sequencing was employed to analyze 44,206 cells from tumor and adjacent normal tissues of ESCC patients, identifying distinct cell types and their transcriptional shifts. We conducted differential gene expression analysis to assess changes within the tumor microenvironment (TME). Validation of key regulatory interactions was performed using qPCR in a cohort of 21 ESCC patients and further substantiated through experimental assays in ESCC cell lines. Results The study revealed critical alterations in cell composition and gene expression across identified cell populations, with a notable shift towards pro-tumorigenic states. A significant regulatory influence of STAT3 on LHPP was discovered, establishing a novel aspect of ESCC pathogenesis. Elevated levels of STAT3 and suppressed LHPP expression were validated in clinical samples. Functional assays confirmed that STAT3 directly represses LHPP at the promoter level, and disruption of this interaction by promoter mutations diminished STAT3's repressive effect. Conclusion This investigation underscores the central role of STAT3 as a regulator in ESCC, directly impacting LHPP expression and suggesting a regulatory loop crucial for tumor behavior. The insights gained from our comprehensive cellular and molecular analysis offer a deeper understanding of the dynamics within the ESCC microenvironment. These findings pave the way for targeted therapeutic interventions focusing on the STAT3-LHPP axis, providing a strategic approach to improve ESCC management and prognosis.https://doi.org/10.1186/s10020-024-00962-0ESCCSingle-cell transcriptomicsTumor microenvironmentSTAT3LHPP |
| spellingShingle | Yurao Chen Zemao Zheng Luoshai Wang Ronghuai Chen Ming He Xiang Zhao Liyan Jin Juan Yao Deciphering STAT3’s negative regulation of LHPP in ESCC progression through single-cell transcriptomics analysis Molecular Medicine ESCC Single-cell transcriptomics Tumor microenvironment STAT3 LHPP |
| title | Deciphering STAT3’s negative regulation of LHPP in ESCC progression through single-cell transcriptomics analysis |
| title_full | Deciphering STAT3’s negative regulation of LHPP in ESCC progression through single-cell transcriptomics analysis |
| title_fullStr | Deciphering STAT3’s negative regulation of LHPP in ESCC progression through single-cell transcriptomics analysis |
| title_full_unstemmed | Deciphering STAT3’s negative regulation of LHPP in ESCC progression through single-cell transcriptomics analysis |
| title_short | Deciphering STAT3’s negative regulation of LHPP in ESCC progression through single-cell transcriptomics analysis |
| title_sort | deciphering stat3 s negative regulation of lhpp in escc progression through single cell transcriptomics analysis |
| topic | ESCC Single-cell transcriptomics Tumor microenvironment STAT3 LHPP |
| url | https://doi.org/10.1186/s10020-024-00962-0 |
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