Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma.
Sci Rep. 2025 Apr 22; 15(1):13955.SR

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.

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Authors+Show Affiliations

Shang Y

PET-CT Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China. Future Technology Institute, Xi'an Jiaotong University, Xi'an, 710049, Shaanxi, China.

Liang Y

Department of Physical Examination, The First Hospital Affiliated to Xi'an Jiao Tong University, Xi'an, 710061, Shaanxi, China.

Zhang B

Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.

Wu W

Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.

Peng Y

Future Technology Institute, Xi'an Jiaotong University, Xi'an, 710049, Shaanxi, China.

Wang J

Future Technology Institute, Xi'an Jiaotong University, Xi'an, 710049, Shaanxi, China.

Zhang M

Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China. zhangming01@xjtu.edu.cn.

Niu C

PET-CT Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China. niuchen1984@163.com. Future Technology Institute, Xi'an Jiaotong University, Xi'an, 710049, Shaanxi, China. niuchen1984@163.com. Department of Information, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China. niuchen1984@163.com.

MeSH

GlioblastomaHumansDrug Resistance, NeoplasmNF-kappa BCell Adhesion MoleculesSignal TransductionCell Line, TumorEpithelial-Mesenchymal TransitionTemozolomideAnimalsBrain NeoplasmsCell ProliferationMiceCell MovementGene Expression Regulation, NeoplasticDisease ProgressionPeriostin

Pub Type(s)

Journal Article

Language

eng

PubMed ID

40263417

Citation

Shang, Yu, et al. "Periostin-mediated Activation of NF-κB Signaling Promotes Tumor Progression and Chemoresistance in Glioblastoma." Scientific Reports, vol. 15, no. 1, 2025, p. 13955.

Shang Y, Liang Y, Zhang B, et al. Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma. Sci Rep. 2025;15(1):13955.

Shang, Y., Liang, Y., Zhang, B., Wu, W., Peng, Y., Wang, J., Zhang, M., & Niu, C. (2025). Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma. Scientific Reports, 15(1), 13955. https://doi.org/10.1038/s41598-025-92969-8

Shang Y, et al. Periostin-mediated Activation of NF-κB Signaling Promotes Tumor Progression and Chemoresistance in Glioblastoma. Sci Rep. 2025 Apr 22;15(1):13955. PubMed PMID: 40263417.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma. AU - Shang,Yu, AU - Liang,Yuxia, AU - Zhang,Beichen, AU - Wu,Wei, AU - Peng,Yihao, AU - Wang,Jin, AU - Zhang,Ming, AU - Niu,Chen, Y1 - 2025/04/22/ PY - 2024/09/10/received PY - 2025/03/04/accepted PY - 2025/4/23/medline PY - 2025/4/23/pubmed PY - 2025/4/22/entrez KW - EMT-related phenotypes KW - Glioblastoma KW - NF-κB signaling KW - POSTN KW - TMZ resistance SP - 13955 EP - 13955 JF - Scientific reports JO - Sci Rep VL - 15 IS - 1 N2 - 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. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/40263417/Periostin_mediated_activation_of_NF_ DB - PRIME DP - Unbound Medicine ER -

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Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma.Sci Rep. 2025 Apr 22; 15(1):13955.SR