Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma
Abstract Glioblastoma (GBM) is the most aggressive form of diffuse glioma, characterized by high lethality. Temozolomide (TMZ)-based chemotherapy is a standard treatment for GBM, but development of chemoresistance poses a significant therapeutic challenge. Despite advances in understanding GBM biolo...
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Nature Portfolio
2025-04-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-92969-8 |
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| author | Yu Shang Yuxia Liang Beichen Zhang Wei Wu Yihao Peng Jin Wang Ming Zhang Chen Niu |
| author_facet | Yu Shang Yuxia Liang Beichen Zhang Wei Wu Yihao Peng Jin Wang Ming Zhang Chen Niu |
| author_sort | Yu Shang |
| collection | DOAJ |
| description | Abstract Glioblastoma (GBM) is the most aggressive form of diffuse glioma, characterized by high lethality. Temozolomide (TMZ)-based chemotherapy is a standard treatment for GBM, but development of chemoresistance poses a significant therapeutic challenge. Despite advances in understanding GBM biology, the mechanisms driving TMZ resistance remain unclear. Identifying vital molecular players involved in this resistance is crucial for developing new therapies. Our results indicated that periostin (POSTN) was significantly upregulated in GBM cell lines and patient samples, correlating with poorer clinical outcomes. POSTN overexpression enhanced GBM cell proliferation, migration, invasion, and chemoresistance, while lentiviral suppression of POSTN significantly reduced these behaviors. In vivo, bioluminescence imaging further confirmed the enhanced tumor growth associated with POSTN overexpression. Bioinformatics analysis was performed to explore the underlying molecular mechanism. The results revealed a strong correlation between POSTN and epithelial-mesenchymal transition (EMT) process and the tumor necrosis factor α (TNFα)-NF-κB signaling pathway. Moreover, exogenous POSTN silencing reduced IκB-kinase α (IKKα) phosphorylation, thereby decreasing NF-κB expression by limiting IκBα degradation. Collectively, our study demonstrated that POSTN-induced activation of NF-κB signaling and EMT processes promoted the malignancy and chemoresistance of GBM, suggesting that POSTN may serve as a reliable prognostic biomarker and potential therapeutic target for GBM. |
| format | Article |
| id | doaj-art-5e676e81a694491f936dc7282df2a28a |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-5e676e81a694491f936dc7282df2a28a2025-08-20T03:14:06ZengNature PortfolioScientific Reports2045-23222025-04-0115111510.1038/s41598-025-92969-8Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastomaYu Shang0Yuxia Liang1Beichen Zhang2Wei Wu3Yihao Peng4Jin Wang5Ming Zhang6Chen Niu7PET-CT Center, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Physical Examination, The First Hospital Affiliated to Xi’an Jiao Tong UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityFuture Technology Institute, Xi’an Jiaotong UniversityFuture Technology Institute, Xi’an Jiaotong UniversityDepartment of Radiology, The First Affiliated Hospital of Xi’an Jiaotong UniversityPET-CT Center, The First Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Glioblastoma (GBM) is the most aggressive form of diffuse glioma, characterized by high lethality. Temozolomide (TMZ)-based chemotherapy is a standard treatment for GBM, but development of chemoresistance poses a significant therapeutic challenge. Despite advances in understanding GBM biology, the mechanisms driving TMZ resistance remain unclear. Identifying vital molecular players involved in this resistance is crucial for developing new therapies. Our results indicated that periostin (POSTN) was significantly upregulated in GBM cell lines and patient samples, correlating with poorer clinical outcomes. POSTN overexpression enhanced GBM cell proliferation, migration, invasion, and chemoresistance, while lentiviral suppression of POSTN significantly reduced these behaviors. In vivo, bioluminescence imaging further confirmed the enhanced tumor growth associated with POSTN overexpression. Bioinformatics analysis was performed to explore the underlying molecular mechanism. The results revealed a strong correlation between POSTN and epithelial-mesenchymal transition (EMT) process and the tumor necrosis factor α (TNFα)-NF-κB signaling pathway. Moreover, exogenous POSTN silencing reduced IκB-kinase α (IKKα) phosphorylation, thereby decreasing NF-κB expression by limiting IκBα degradation. Collectively, our study demonstrated that POSTN-induced activation of NF-κB signaling and EMT processes promoted the malignancy and chemoresistance of GBM, suggesting that POSTN may serve as a reliable prognostic biomarker and potential therapeutic target for GBM.https://doi.org/10.1038/s41598-025-92969-8EMT-related phenotypesNF-κB signalingTMZ resistancePOSTNGlioblastoma |
| spellingShingle | Yu Shang Yuxia Liang Beichen Zhang Wei Wu Yihao Peng Jin Wang Ming Zhang Chen Niu Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma Scientific Reports EMT-related phenotypes NF-κB signaling TMZ resistance POSTN Glioblastoma |
| title | Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma |
| title_full | Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma |
| title_fullStr | Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma |
| title_full_unstemmed | Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma |
| title_short | Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma |
| title_sort | periostin mediated activation of nf κb signaling promotes tumor progression and chemoresistance in glioblastoma |
| topic | EMT-related phenotypes NF-κB signaling TMZ resistance POSTN Glioblastoma |
| url | https://doi.org/10.1038/s41598-025-92969-8 |
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