CCAAT/enhancer-binding protein delta regulates the stemness of glioma stem-like cells through activating PDGFA expression upon inflammatory stimulation

Shao Ming Wang, Hong Yi Lin, Yen Lin Chen, Tsung I. Hsu, Jian Ying Chuang, Tzu Jen Kao, Chiung Yuan Ko

研究成果: 雜誌貢獻文章

摘要

Background: The small population of glioma stem-like cells (GSCs) contributes to tumor initiation, malignancy, and recurrence in glioblastoma. However, the maintenance of GSC properties in the tumor microenvironment remains unclear. In glioma, non-neoplastic cells create an inflammatory environment and subsequently mediate tumor progression and maintenance. Transcriptional factor CCAAT/enhancer-binding protein delta (CEBPD) is suggested to regulate various genes responsive to inflammatory cytokines, thus prompting us to investigate its role in regulating GSCs stemness after inflammatory stimulation. Methods: Stemness properties were analyzed by using spheroid formation. Oncomine and TCGA bioinformatic databases were used to analyze gene expression. Western blotting, quantitative real-time polymerase chain reaction, luciferase reporter assay, and chromatin immunoprecipitation assay were used to analyze proteins and gene transcript levels. The glioma tissue microarrays were used for CEBPD and PDGFA expression by immunohistochemistry staining. Results: We first found that IL-1β promotes glioma spheroid formation and is associated with elevated CEBPD expression. Using microarray analysis, platelet-derived growth factor subunit A (PDGFA) was confirmed as a CEBPD-regulated gene that mediates IL-1β-enhanced GSCs self-renewal. Further analysis of the genomic database and tissue array revealed that the expression levels between CEBPD and PDGFA were coincident in glioma patient samples. Conclusion: This is the first report showing the activation of PDGFA expression by CEBPD through IL-1β treatment and a novel CEBPD function in maintaining the self-renewal feature of GSCs.

原文英語
文章編號146
期刊Journal of Neuroinflammation
16
發行號1
DOIs
出版狀態已發佈 - 七月 12 2019

指紋

CCAAT-Enhancer-Binding Protein-delta
Platelet-Derived Growth Factor
Glioma
Stem Cells
Interleukin-1
Maintenance
Databases
Neoplasms
Tumor Microenvironment
Chromatin Immunoprecipitation
Glioblastoma
Microarray Analysis
Computational Biology
Luciferases
Genes
Real-Time Polymerase Chain Reaction

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

引用此文

@article{82d28bfe2c9b420fbccfdc4481fcb5d0,
title = "CCAAT/enhancer-binding protein delta regulates the stemness of glioma stem-like cells through activating PDGFA expression upon inflammatory stimulation",
abstract = "Background: The small population of glioma stem-like cells (GSCs) contributes to tumor initiation, malignancy, and recurrence in glioblastoma. However, the maintenance of GSC properties in the tumor microenvironment remains unclear. In glioma, non-neoplastic cells create an inflammatory environment and subsequently mediate tumor progression and maintenance. Transcriptional factor CCAAT/enhancer-binding protein delta (CEBPD) is suggested to regulate various genes responsive to inflammatory cytokines, thus prompting us to investigate its role in regulating GSCs stemness after inflammatory stimulation. Methods: Stemness properties were analyzed by using spheroid formation. Oncomine and TCGA bioinformatic databases were used to analyze gene expression. Western blotting, quantitative real-time polymerase chain reaction, luciferase reporter assay, and chromatin immunoprecipitation assay were used to analyze proteins and gene transcript levels. The glioma tissue microarrays were used for CEBPD and PDGFA expression by immunohistochemistry staining. Results: We first found that IL-1β promotes glioma spheroid formation and is associated with elevated CEBPD expression. Using microarray analysis, platelet-derived growth factor subunit A (PDGFA) was confirmed as a CEBPD-regulated gene that mediates IL-1β-enhanced GSCs self-renewal. Further analysis of the genomic database and tissue array revealed that the expression levels between CEBPD and PDGFA were coincident in glioma patient samples. Conclusion: This is the first report showing the activation of PDGFA expression by CEBPD through IL-1β treatment and a novel CEBPD function in maintaining the self-renewal feature of GSCs.",
keywords = "CEBPD, Glioblastoma multiforme, Glioma stem-like cell, Inflammation, Interleukin-1β, PDGFA",
author = "Wang, {Shao Ming} and Lin, {Hong Yi} and Chen, {Yen Lin} and Hsu, {Tsung I.} and Chuang, {Jian Ying} and Kao, {Tzu Jen} and Ko, {Chiung Yuan}",
year = "2019",
month = "7",
day = "12",
doi = "10.1186/s12974-019-1535-z",
language = "English",
volume = "16",
journal = "Journal of Neuroinflammation",
issn = "1742-2094",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - CCAAT/enhancer-binding protein delta regulates the stemness of glioma stem-like cells through activating PDGFA expression upon inflammatory stimulation

AU - Wang, Shao Ming

AU - Lin, Hong Yi

AU - Chen, Yen Lin

AU - Hsu, Tsung I.

AU - Chuang, Jian Ying

AU - Kao, Tzu Jen

AU - Ko, Chiung Yuan

PY - 2019/7/12

Y1 - 2019/7/12

N2 - Background: The small population of glioma stem-like cells (GSCs) contributes to tumor initiation, malignancy, and recurrence in glioblastoma. However, the maintenance of GSC properties in the tumor microenvironment remains unclear. In glioma, non-neoplastic cells create an inflammatory environment and subsequently mediate tumor progression and maintenance. Transcriptional factor CCAAT/enhancer-binding protein delta (CEBPD) is suggested to regulate various genes responsive to inflammatory cytokines, thus prompting us to investigate its role in regulating GSCs stemness after inflammatory stimulation. Methods: Stemness properties were analyzed by using spheroid formation. Oncomine and TCGA bioinformatic databases were used to analyze gene expression. Western blotting, quantitative real-time polymerase chain reaction, luciferase reporter assay, and chromatin immunoprecipitation assay were used to analyze proteins and gene transcript levels. The glioma tissue microarrays were used for CEBPD and PDGFA expression by immunohistochemistry staining. Results: We first found that IL-1β promotes glioma spheroid formation and is associated with elevated CEBPD expression. Using microarray analysis, platelet-derived growth factor subunit A (PDGFA) was confirmed as a CEBPD-regulated gene that mediates IL-1β-enhanced GSCs self-renewal. Further analysis of the genomic database and tissue array revealed that the expression levels between CEBPD and PDGFA were coincident in glioma patient samples. Conclusion: This is the first report showing the activation of PDGFA expression by CEBPD through IL-1β treatment and a novel CEBPD function in maintaining the self-renewal feature of GSCs.

AB - Background: The small population of glioma stem-like cells (GSCs) contributes to tumor initiation, malignancy, and recurrence in glioblastoma. However, the maintenance of GSC properties in the tumor microenvironment remains unclear. In glioma, non-neoplastic cells create an inflammatory environment and subsequently mediate tumor progression and maintenance. Transcriptional factor CCAAT/enhancer-binding protein delta (CEBPD) is suggested to regulate various genes responsive to inflammatory cytokines, thus prompting us to investigate its role in regulating GSCs stemness after inflammatory stimulation. Methods: Stemness properties were analyzed by using spheroid formation. Oncomine and TCGA bioinformatic databases were used to analyze gene expression. Western blotting, quantitative real-time polymerase chain reaction, luciferase reporter assay, and chromatin immunoprecipitation assay were used to analyze proteins and gene transcript levels. The glioma tissue microarrays were used for CEBPD and PDGFA expression by immunohistochemistry staining. Results: We first found that IL-1β promotes glioma spheroid formation and is associated with elevated CEBPD expression. Using microarray analysis, platelet-derived growth factor subunit A (PDGFA) was confirmed as a CEBPD-regulated gene that mediates IL-1β-enhanced GSCs self-renewal. Further analysis of the genomic database and tissue array revealed that the expression levels between CEBPD and PDGFA were coincident in glioma patient samples. Conclusion: This is the first report showing the activation of PDGFA expression by CEBPD through IL-1β treatment and a novel CEBPD function in maintaining the self-renewal feature of GSCs.

KW - CEBPD

KW - Glioblastoma multiforme

KW - Glioma stem-like cell

KW - Inflammation

KW - Interleukin-1β

KW - PDGFA

UR - http://www.scopus.com/inward/record.url?scp=85068929632&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068929632&partnerID=8YFLogxK

U2 - 10.1186/s12974-019-1535-z

DO - 10.1186/s12974-019-1535-z

M3 - Article

VL - 16

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

SN - 1742-2094

IS - 1

M1 - 146

ER -