Single-cell profiling of SLC family transporters: uncovering the role of SLC7A1 in osteosarcoma
Abstract Background Osteosarcoma is the most common malignant bone tumor in children and adolescents, characterized by high disability and mortality rates. Over the past three decades, therapeutic outcomes have plateaued, underscoring the critical need for innovative therapeutic targets. Solute carr...
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2025-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06086-1 |
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| author | Yan Liao Junkai Chen Hao Yao Ting Zheng Jian Tu Weidong Chen ZeHao Guo Yutong Zou Lili Wen Xianbiao Xie |
| author_facet | Yan Liao Junkai Chen Hao Yao Ting Zheng Jian Tu Weidong Chen ZeHao Guo Yutong Zou Lili Wen Xianbiao Xie |
| author_sort | Yan Liao |
| collection | DOAJ |
| description | Abstract Background Osteosarcoma is the most common malignant bone tumor in children and adolescents, characterized by high disability and mortality rates. Over the past three decades, therapeutic outcomes have plateaued, underscoring the critical need for innovative therapeutic targets. Solute carrier (SLC) family transporters have been implicated in the malignant progression of a variety of tumors, however, their specific role in osteosarcoma remains poorly understood. Methods The single-cell sequencing data from GSE152048 and GSE162454, along with RNA-seq from the TARGET and GSE21257 cohorts, were utilized for the analysis in this study. LASSO regression analysis was conducted to identify prognostic genes and construct an SLC-related prognostic signature. Survival analysis and ROC analysis evaluated the validity of the prognostic signature. The ESTIMATE and CIBERSORT Packages were utilized to assess the immune infiltration status. Pseudotime and CellChat analyses were performed to investigate the relationship between SLC7A1, malignant phenotypes, and the immune microenvironment. CCK8 assays, EdU staining, colony formation assays, Transwell assays, and co-culture systems were used to assess the effects of SLC7A1 on cell proliferation, metastasis, and macrophage polarization. Finally, virtual docking identified potential drugs targeting SLC7A1. Results SLCs displayed distinct expression patterns across various cell types within the osteosarcoma microenvironment, with myeloid cells exhibiting a preference for amino acid uptake. A prognostic model comprising nine genes was constructed via LASSO regression, with SLC7A1 showing the highest hazard ratio. Multiple analytical algorithms indicated that SLCs were associated with immune cell infiltration and immune checkpoint gene expression. Single-cell analysis indicated that SLC7A1 was predominantly expressed in osteosarcoma cells and correlated with various malignant tumor characteristics. SLC7A1 also regulate interactions between tumor cells and macrophages, as well as modulate macrophage function through multiple pathways. In vitro assays and survival analysis demonstrated that inhibition of SLC7A1 suppressed the malignant phenotype of osteosarcoma cells, with SLC7A1 expression correlating with poor prognosis. Co-culture models confirmed the involvement of SLC7A1 in macrophage polarization. Finally, virtual screening and CETSA identified Cepharanthine as potential inhibitors of SLC7A1. Conclusion SLC-related prognostic signatures can be utilized for the prognostic evaluation of osteosarcoma. Pharmacological inhibition of SLC7A1 may be a feasible therapeutic approach for osteosarcoma. |
| format | Article |
| id | doaj-art-bbbee271cfa242d58cbab24427f37e0e |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj-art-bbbee271cfa242d58cbab24427f37e0e2025-01-26T12:50:27ZengBMCJournal of Translational Medicine1479-58762025-01-0123112110.1186/s12967-025-06086-1Single-cell profiling of SLC family transporters: uncovering the role of SLC7A1 in osteosarcomaYan Liao0Junkai Chen1Hao Yao2Ting Zheng3Jian Tu4Weidong Chen5ZeHao Guo6Yutong Zou7Lili Wen8Xianbiao Xie9Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen UniversityThe Affiliated Guangzhou Twelfth People’s Hospital, Guangzhou Medical UniversityDepartment of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Anesthesiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer CenterDepartment of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen UniversityAbstract Background Osteosarcoma is the most common malignant bone tumor in children and adolescents, characterized by high disability and mortality rates. Over the past three decades, therapeutic outcomes have plateaued, underscoring the critical need for innovative therapeutic targets. Solute carrier (SLC) family transporters have been implicated in the malignant progression of a variety of tumors, however, their specific role in osteosarcoma remains poorly understood. Methods The single-cell sequencing data from GSE152048 and GSE162454, along with RNA-seq from the TARGET and GSE21257 cohorts, were utilized for the analysis in this study. LASSO regression analysis was conducted to identify prognostic genes and construct an SLC-related prognostic signature. Survival analysis and ROC analysis evaluated the validity of the prognostic signature. The ESTIMATE and CIBERSORT Packages were utilized to assess the immune infiltration status. Pseudotime and CellChat analyses were performed to investigate the relationship between SLC7A1, malignant phenotypes, and the immune microenvironment. CCK8 assays, EdU staining, colony formation assays, Transwell assays, and co-culture systems were used to assess the effects of SLC7A1 on cell proliferation, metastasis, and macrophage polarization. Finally, virtual docking identified potential drugs targeting SLC7A1. Results SLCs displayed distinct expression patterns across various cell types within the osteosarcoma microenvironment, with myeloid cells exhibiting a preference for amino acid uptake. A prognostic model comprising nine genes was constructed via LASSO regression, with SLC7A1 showing the highest hazard ratio. Multiple analytical algorithms indicated that SLCs were associated with immune cell infiltration and immune checkpoint gene expression. Single-cell analysis indicated that SLC7A1 was predominantly expressed in osteosarcoma cells and correlated with various malignant tumor characteristics. SLC7A1 also regulate interactions between tumor cells and macrophages, as well as modulate macrophage function through multiple pathways. In vitro assays and survival analysis demonstrated that inhibition of SLC7A1 suppressed the malignant phenotype of osteosarcoma cells, with SLC7A1 expression correlating with poor prognosis. Co-culture models confirmed the involvement of SLC7A1 in macrophage polarization. Finally, virtual screening and CETSA identified Cepharanthine as potential inhibitors of SLC7A1. Conclusion SLC-related prognostic signatures can be utilized for the prognostic evaluation of osteosarcoma. Pharmacological inhibition of SLC7A1 may be a feasible therapeutic approach for osteosarcoma.https://doi.org/10.1186/s12967-025-06086-1OsteosarcomaSolute carrier (SLC) family transportersTumor immune microenvironmentSLC7A1TAMs |
| spellingShingle | Yan Liao Junkai Chen Hao Yao Ting Zheng Jian Tu Weidong Chen ZeHao Guo Yutong Zou Lili Wen Xianbiao Xie Single-cell profiling of SLC family transporters: uncovering the role of SLC7A1 in osteosarcoma Journal of Translational Medicine Osteosarcoma Solute carrier (SLC) family transporters Tumor immune microenvironment SLC7A1 TAMs |
| title | Single-cell profiling of SLC family transporters: uncovering the role of SLC7A1 in osteosarcoma |
| title_full | Single-cell profiling of SLC family transporters: uncovering the role of SLC7A1 in osteosarcoma |
| title_fullStr | Single-cell profiling of SLC family transporters: uncovering the role of SLC7A1 in osteosarcoma |
| title_full_unstemmed | Single-cell profiling of SLC family transporters: uncovering the role of SLC7A1 in osteosarcoma |
| title_short | Single-cell profiling of SLC family transporters: uncovering the role of SLC7A1 in osteosarcoma |
| title_sort | single cell profiling of slc family transporters uncovering the role of slc7a1 in osteosarcoma |
| topic | Osteosarcoma Solute carrier (SLC) family transporters Tumor immune microenvironment SLC7A1 TAMs |
| url | https://doi.org/10.1186/s12967-025-06086-1 |
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