Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma
The mesenchymal (MES) phenotype of glioblastoma (GBM) is the most aggressive and therapy-resistant subtype of GBM. The MES phenotype transition during tumor progression results from both tumor-intrinsic genetic alterations and tumor-extrinsic microenvironmental factors. In this study, we sought to i...
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MDPI AG
2024-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/4/840 |
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| author | Zaixiang Fu Zihang Chen Jingya Ye Jianxiong Ji Weifang Ni Weibo Lin Haopu Lin Liquan Lu Ganggui Zhu Qin Xie Feng Yan Gao Chen Fuyi Liu |
| author_facet | Zaixiang Fu Zihang Chen Jingya Ye Jianxiong Ji Weifang Ni Weibo Lin Haopu Lin Liquan Lu Ganggui Zhu Qin Xie Feng Yan Gao Chen Fuyi Liu |
| author_sort | Zaixiang Fu |
| collection | DOAJ |
| description | The mesenchymal (MES) phenotype of glioblastoma (GBM) is the most aggressive and therapy-resistant subtype of GBM. The MES phenotype transition during tumor progression results from both tumor-intrinsic genetic alterations and tumor-extrinsic microenvironmental factors. In this study, we sought to identify genes that can modulate the MES phenotype via both mechanisms. By integrating weighted gene co-expression network analysis (WGCNA) and the differential expression analysis of hypoxia-immunosuppression-related genes, we identified the plasminogen activator, urokinase receptor (PLAUR) as the hub gene. Functional enrichment analysis and GSVA analysis demonstrated that PLAUR was associated with the MES phenotype of glioma and the hypoxia-immunosuppression-related microenvironmental components. Single-cell sequencing analysis revealed that PLAUR mediated the ligand–receptor interaction between tumor-associated macrophages (TAMs) and glioma cells. Functional experiments in vitro with cell lines or primary glioma cells and xenograft models using BALB/c nude mice confirmed the role of PLAUR in promoting the MES phenotype of GBM. Our findings indicate that PLAUR regulates both glioma cells and tumor cell-extrinsic factors that favor the MES phenotype and suggest that PLAUR might be a potential target for GBM therapy. |
| first_indexed | 2024-03-07T22:38:23Z |
| format | Article |
| id | doaj.art-19e67649fb8f478bb57b329f38e472de |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-07T22:38:23Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-19e67649fb8f478bb57b329f38e472de2024-02-23T15:11:24ZengMDPI AGCancers2072-66942024-02-0116484010.3390/cancers16040840Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of GlioblastomaZaixiang Fu0Zihang Chen1Jingya Ye2Jianxiong Ji3Weifang Ni4Weibo Lin5Haopu Lin6Liquan Lu7Ganggui Zhu8Qin Xie9Feng Yan10Gao Chen11Fuyi Liu12Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Lung Transplantation, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310052, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaThe mesenchymal (MES) phenotype of glioblastoma (GBM) is the most aggressive and therapy-resistant subtype of GBM. The MES phenotype transition during tumor progression results from both tumor-intrinsic genetic alterations and tumor-extrinsic microenvironmental factors. In this study, we sought to identify genes that can modulate the MES phenotype via both mechanisms. By integrating weighted gene co-expression network analysis (WGCNA) and the differential expression analysis of hypoxia-immunosuppression-related genes, we identified the plasminogen activator, urokinase receptor (PLAUR) as the hub gene. Functional enrichment analysis and GSVA analysis demonstrated that PLAUR was associated with the MES phenotype of glioma and the hypoxia-immunosuppression-related microenvironmental components. Single-cell sequencing analysis revealed that PLAUR mediated the ligand–receptor interaction between tumor-associated macrophages (TAMs) and glioma cells. Functional experiments in vitro with cell lines or primary glioma cells and xenograft models using BALB/c nude mice confirmed the role of PLAUR in promoting the MES phenotype of GBM. Our findings indicate that PLAUR regulates both glioma cells and tumor cell-extrinsic factors that favor the MES phenotype and suggest that PLAUR might be a potential target for GBM therapy.https://www.mdpi.com/2072-6694/16/4/840glioblastomaPLAURtumor microenvironmentmesenchymal phenotypesingle-cell RNA sequencing |
| spellingShingle | Zaixiang Fu Zihang Chen Jingya Ye Jianxiong Ji Weifang Ni Weibo Lin Haopu Lin Liquan Lu Ganggui Zhu Qin Xie Feng Yan Gao Chen Fuyi Liu Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma Cancers glioblastoma PLAUR tumor microenvironment mesenchymal phenotype single-cell RNA sequencing |
| title | Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma |
| title_full | Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma |
| title_fullStr | Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma |
| title_full_unstemmed | Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma |
| title_short | Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma |
| title_sort | identifying plaur as a pivotal gene of tumor microenvironment and regulating mesenchymal phenotype of glioblastoma |
| topic | glioblastoma PLAUR tumor microenvironment mesenchymal phenotype single-cell RNA sequencing |
| url | https://www.mdpi.com/2072-6694/16/4/840 |
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