Pleiotrophin promote glioma proliferation and invasion by enhancing NF-κB/SLUG mediated epithelial–mesenchymal transition
Abstract Background Gliomas are aggressive brain tumors with high mortality and recurrence rates. Pleiotrophin (PTN), a cytokine that interacts with heparin, is upregulated in several cancers, including breast and lung cancer. PTN is implicated in cancer progression, recurrence, epithelial–mesenchym...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02808-9 |
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| author | Hong-Xing Ye Chao Zhang Long-Yuan He Ping Lan Feng Wang Ren-Ya Zhan Xiu-Jue Zheng |
| author_facet | Hong-Xing Ye Chao Zhang Long-Yuan He Ping Lan Feng Wang Ren-Ya Zhan Xiu-Jue Zheng |
| author_sort | Hong-Xing Ye |
| collection | DOAJ |
| description | Abstract Background Gliomas are aggressive brain tumors with high mortality and recurrence rates. Pleiotrophin (PTN), a cytokine that interacts with heparin, is upregulated in several cancers, including breast and lung cancer. PTN is implicated in cancer progression, recurrence, epithelial–mesenchymal transition (EMT), and metastasis. However, the role of PTN in glioma progression remains poorly understood. This study aimed to investigate the expression profile of PTN in glioma and its potential prognostic significance. Methods The expression levels of PTN in glioma samples were analyzed using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). Gene Ontology (GO) term analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to identify PTN-associated pathways. In vitro experiments were performed to assess the impact of PTN suppression on glioma cell growth, cell cycle progression, migration, and invasion. In addition, gene set enrichment analysis (GSEA) and Western blot were employed to investigate the link between PTN and NF-κB signaling pathways. Results PTN expression was significantly higher in glioma samples, and elevated PTN levels were associated with decreased overall survival. GO term and KEGG analysis showed that PTN is primarily linked to pathways related to cell mitosis, including the cell cycle and DNA replication. In vitro experiments demonstrated that the suppression of PTN inhibited glioma cell growth, arrested the cell cycle in the G0/G1 phase, and impaired the migratory and invasive capabilities of glioma cells. GSEA revealed a significant correlation between PTN and the NF-κB pathway. Further investigation showed that PTN suppression inhibited NF-κB activation and IκB phosphorylation, thereby preventing Slug-induced EMT in glioma cells. Conclusions PTN plays a crucial role in glioma progression by regulating cell proliferation, migration, invasion, and EMT through the NF-κB pathway. PTN may serve as an important prognostic biomarker and therapeutic target in glioma treatment. |
| format | Article |
| id | doaj-art-da8e13c0ffb1418bb45c30db1fcaaf98 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-da8e13c0ffb1418bb45c30db1fcaaf982025-08-20T04:01:25ZengBMCEuropean Journal of Medical Research2047-783X2025-07-0130111210.1186/s40001-025-02808-9Pleiotrophin promote glioma proliferation and invasion by enhancing NF-κB/SLUG mediated epithelial–mesenchymal transitionHong-Xing Ye0Chao Zhang1Long-Yuan He2Ping Lan3Feng Wang4Ren-Ya Zhan5Xiu-Jue Zheng6Department of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of MedicineZhejiang University School of MedicineDepartment of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of MedicineAbstract Background Gliomas are aggressive brain tumors with high mortality and recurrence rates. Pleiotrophin (PTN), a cytokine that interacts with heparin, is upregulated in several cancers, including breast and lung cancer. PTN is implicated in cancer progression, recurrence, epithelial–mesenchymal transition (EMT), and metastasis. However, the role of PTN in glioma progression remains poorly understood. This study aimed to investigate the expression profile of PTN in glioma and its potential prognostic significance. Methods The expression levels of PTN in glioma samples were analyzed using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). Gene Ontology (GO) term analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to identify PTN-associated pathways. In vitro experiments were performed to assess the impact of PTN suppression on glioma cell growth, cell cycle progression, migration, and invasion. In addition, gene set enrichment analysis (GSEA) and Western blot were employed to investigate the link between PTN and NF-κB signaling pathways. Results PTN expression was significantly higher in glioma samples, and elevated PTN levels were associated with decreased overall survival. GO term and KEGG analysis showed that PTN is primarily linked to pathways related to cell mitosis, including the cell cycle and DNA replication. In vitro experiments demonstrated that the suppression of PTN inhibited glioma cell growth, arrested the cell cycle in the G0/G1 phase, and impaired the migratory and invasive capabilities of glioma cells. GSEA revealed a significant correlation between PTN and the NF-κB pathway. Further investigation showed that PTN suppression inhibited NF-κB activation and IκB phosphorylation, thereby preventing Slug-induced EMT in glioma cells. Conclusions PTN plays a crucial role in glioma progression by regulating cell proliferation, migration, invasion, and EMT through the NF-κB pathway. PTN may serve as an important prognostic biomarker and therapeutic target in glioma treatment.https://doi.org/10.1186/s40001-025-02808-9PleiotrophinGliomaProliferation and invasionNF-κB pathwayEpithelial–mesenchymal transition |
| spellingShingle | Hong-Xing Ye Chao Zhang Long-Yuan He Ping Lan Feng Wang Ren-Ya Zhan Xiu-Jue Zheng Pleiotrophin promote glioma proliferation and invasion by enhancing NF-κB/SLUG mediated epithelial–mesenchymal transition European Journal of Medical Research Pleiotrophin Glioma Proliferation and invasion NF-κB pathway Epithelial–mesenchymal transition |
| title | Pleiotrophin promote glioma proliferation and invasion by enhancing NF-κB/SLUG mediated epithelial–mesenchymal transition |
| title_full | Pleiotrophin promote glioma proliferation and invasion by enhancing NF-κB/SLUG mediated epithelial–mesenchymal transition |
| title_fullStr | Pleiotrophin promote glioma proliferation and invasion by enhancing NF-κB/SLUG mediated epithelial–mesenchymal transition |
| title_full_unstemmed | Pleiotrophin promote glioma proliferation and invasion by enhancing NF-κB/SLUG mediated epithelial–mesenchymal transition |
| title_short | Pleiotrophin promote glioma proliferation and invasion by enhancing NF-κB/SLUG mediated epithelial–mesenchymal transition |
| title_sort | pleiotrophin promote glioma proliferation and invasion by enhancing nf κb slug mediated epithelial mesenchymal transition |
| topic | Pleiotrophin Glioma Proliferation and invasion NF-κB pathway Epithelial–mesenchymal transition |
| url | https://doi.org/10.1186/s40001-025-02808-9 |
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