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Non-canonical NLRC4 inflammasomes in astrocytes contribute to glioma malignancy

Authors
 JeongMin Sim  ;  Ju Won Ahn  ;  JeongMan Park  ;  Yu Jin Kim  ;  Ju-Yeon Jeong  ;  Ji Min Lee  ;  Kyunggi Cho  ;  Hee Jung Ahn  ;  Kyoung Su Sung  ;  Jong-Seok Moon  ;  Ju Hyung Moon  ;  Jaejoon Lim 
Citation
 INFLAMMATION RESEARCH, Vol.72(4) : 813-827, 2023-04 
Journal Title
INFLAMMATION RESEARCH
ISSN
 1023-3830 
Issue Date
2023-04
MeSH
Astrocytes / metabolism ; CARD Signaling Adaptor Proteins / metabolism ; Calcium-Binding Proteins / genetics ; Glioma* ; Humans ; Inflammasomes* / metabolism ; Retrospective Studies ; Tumor Microenvironment
Keywords
Glioma ; Glioma malignancy ; Inflammatory response ; Non-canonical NLRC4 inflammasome ; Therapeutic strategy
Abstract
Background: The present study was designed to explore the pathological role of non-canonical NLRC4 inflammasome in glioma.

Methods: This retrospective study included bioinformatical analysis, including survival, gene ontology, ssGSEA, cox regression, IPA and drug repositioning with TCGA and DepMap database. Experimental validations were conducted in glioma patient's sample and evaluated with histological or cellular functional analysis.

Result: Clinical dataset analysis revealed that non-canonical NLRC4 inflammasomes significantly contribute to glioma progression and poor survival rates. Experimental validation was revealed that the expression of non-canonical NLRC4 inflammasomes were co-localized with astrocytes in malignant gliomas, with a sustained clinical correlation observed between astrocytes and inflammasome signatures. Indeed, the formation of an inflammatory microenvironment increased in malignant gliomas, leading to pyroptosis, known as inflammatory cell death. Molecular interaction analysis revealed that NF-κB pathways potentially serve as the connecting point between the canonical and noncanonical pathways of the NLRC4 inflammasome. Finally, drug repositioning analysis of non-canonical NLRC4 inflammasome-associated molecules revealed that MK-5108, PF4981517, and CTEP may represent effective options for glioma therapy.

Conclusion: The findings of this study suggest that non-canonical NLRC4 inflammasomes contribute to poor prognosis in patients with glioma and induce an inflammatory microenvironment. We propose the pathological phenomenon of non-canonical NLRC4 inflammasomes and several therapeutic strategies based on the modulation of the inflammatory tumor microenvironment.
Full Text
https://link.springer.com/article/10.1007/s00011-023-01710-6
DOI
10.1007/s00011-023-01710-6
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Moon, Ju Hyung(문주형)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/196413
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