LAMA3 overexpression enhances proliferation, migration and invasion in esophageal squamous cell carcinoma based on bioinformatics and experimental validation
Abstract Esophageal squamous cell carcinoma (ESCC) is a highly lethal malignancy and remains a major public health burden worldwide, particularly in China, where both incidence and mortality rates are among the highest globally. Recent studies suggest that laminin subunit alpha 3 (LAMA3), a componen...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-08026-x |
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| author | Xia Wu Qian Li Junbin Wang Lei Li Mingtang Zuo Yufeng Cheng |
| author_facet | Xia Wu Qian Li Junbin Wang Lei Li Mingtang Zuo Yufeng Cheng |
| author_sort | Xia Wu |
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| description | Abstract Esophageal squamous cell carcinoma (ESCC) is a highly lethal malignancy and remains a major public health burden worldwide, particularly in China, where both incidence and mortality rates are among the highest globally. Recent studies suggest that laminin subunit alpha 3 (LAMA3), a component of the basement membrane, may promote tumor progression; however, its specific role in ESCC remains unclear. In this study, we analyzed public RNA-sequencing data from TCGA and TIMER to evaluate LAMA3 expression and its clinical relevance in ESCC. We also validated LAMA3 protein and mRNA expression in clinical samples and cell lines using immunohistochemistry and RT-qPCR. Using siRNA, we established LAMA3-knockdown ESCC cell models and assessed cell proliferation, colony formation, migration, and invasion in vitro. LAMA3 expression was 2.4-fold higher in ESCC tumor tissues than in adjacent normal tissues (p < 0.001). High LAMA3 levels were associated with worse overall survival and disease-free survival (p < 0.05). Knockdown of LAMA3 suppressed cell proliferation by 57% (p < 0.001), migration by 49% (p < 0.001), and invasion by 47% (p < 0.001).Pathway enrichment analysis indicated involvement of LAMA3 and its co-expressed genes in cell adhesion, extracellular matrix organization, and the PI3K-AKT pathway. In summary, our results demonstrate that LAMA3 is a major promoter of ESCC progression and a potential biomarker and therapeutic target. |
| format | Article |
| id | doaj-art-178e2bbc595c4422b71afa09ce2d5c6d |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-178e2bbc595c4422b71afa09ce2d5c6d2025-08-20T03:45:52ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-08026-xLAMA3 overexpression enhances proliferation, migration and invasion in esophageal squamous cell carcinoma based on bioinformatics and experimental validationXia Wu0Qian Li1Junbin Wang2Lei Li3Mingtang Zuo4Yufeng Cheng5Department of Radiation Oncology, Qilu Hospital of Shandong UniversityDepartment of Oncology, Shandong Provincial Third Hospital, Shandong UniversityThe Second Clinical Medicine School, Shandong University of Traditional Chinese MedicineDepartment of Oncology, Shandong Provincial Third Hospital, Shandong UniversityDepartment of Oncology, Shandong Provincial Third Hospital, Shandong UniversityDepartment of Radiation Oncology, Qilu Hospital of Shandong UniversityAbstract Esophageal squamous cell carcinoma (ESCC) is a highly lethal malignancy and remains a major public health burden worldwide, particularly in China, where both incidence and mortality rates are among the highest globally. Recent studies suggest that laminin subunit alpha 3 (LAMA3), a component of the basement membrane, may promote tumor progression; however, its specific role in ESCC remains unclear. In this study, we analyzed public RNA-sequencing data from TCGA and TIMER to evaluate LAMA3 expression and its clinical relevance in ESCC. We also validated LAMA3 protein and mRNA expression in clinical samples and cell lines using immunohistochemistry and RT-qPCR. Using siRNA, we established LAMA3-knockdown ESCC cell models and assessed cell proliferation, colony formation, migration, and invasion in vitro. LAMA3 expression was 2.4-fold higher in ESCC tumor tissues than in adjacent normal tissues (p < 0.001). High LAMA3 levels were associated with worse overall survival and disease-free survival (p < 0.05). Knockdown of LAMA3 suppressed cell proliferation by 57% (p < 0.001), migration by 49% (p < 0.001), and invasion by 47% (p < 0.001).Pathway enrichment analysis indicated involvement of LAMA3 and its co-expressed genes in cell adhesion, extracellular matrix organization, and the PI3K-AKT pathway. In summary, our results demonstrate that LAMA3 is a major promoter of ESCC progression and a potential biomarker and therapeutic target.https://doi.org/10.1038/s41598-025-08026-xESCCLAMA3BioinformaticsProliferationMetastasisInvasion |
| spellingShingle | Xia Wu Qian Li Junbin Wang Lei Li Mingtang Zuo Yufeng Cheng LAMA3 overexpression enhances proliferation, migration and invasion in esophageal squamous cell carcinoma based on bioinformatics and experimental validation Scientific Reports ESCC LAMA3 Bioinformatics Proliferation Metastasis Invasion |
| title | LAMA3 overexpression enhances proliferation, migration and invasion in esophageal squamous cell carcinoma based on bioinformatics and experimental validation |
| title_full | LAMA3 overexpression enhances proliferation, migration and invasion in esophageal squamous cell carcinoma based on bioinformatics and experimental validation |
| title_fullStr | LAMA3 overexpression enhances proliferation, migration and invasion in esophageal squamous cell carcinoma based on bioinformatics and experimental validation |
| title_full_unstemmed | LAMA3 overexpression enhances proliferation, migration and invasion in esophageal squamous cell carcinoma based on bioinformatics and experimental validation |
| title_short | LAMA3 overexpression enhances proliferation, migration and invasion in esophageal squamous cell carcinoma based on bioinformatics and experimental validation |
| title_sort | lama3 overexpression enhances proliferation migration and invasion in esophageal squamous cell carcinoma based on bioinformatics and experimental validation |
| topic | ESCC LAMA3 Bioinformatics Proliferation Metastasis Invasion |
| url | https://doi.org/10.1038/s41598-025-08026-x |
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