Non-canonical NLRC4 inflammasomes in astrocytes contribute to glioma malignancy

by Selleckchem | Apr 04 2023

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.

Comments：

The present study aimed to investigate the role of non-canonical NLRC4 inflammasomes in the progression of glioma, a type of brain tumor. The study utilized a retrospective design, analyzing clinical datasets using bioinformatical methods such as survival analysis, gene ontology analysis, ssGSEA, cox regression, IPA, and drug repositioning. The study also involved experimental validation using histological and cellular functional analysis of glioma patient samples.

The results of the study showed that non-canonical NLRC4 inflammasomes play a significant role in glioma progression and poor survival rates. Experimental validation revealed that the expression of non-canonical NLRC4 inflammasomes was co-localized with astrocytes, and a sustained clinical correlation was observed between astrocytes and inflammasome signatures. The formation of an inflammatory microenvironment in malignant gliomas led to pyroptosis, a type of inflammatory cell death. Molecular interaction analysis suggested that the NF-κB pathway may serve as the connecting point between the canonical and non-canonical pathways of the NLRC4 inflammasome. Finally, drug repositioning analysis revealed that MK-5108, PF4981517, and CTEP may represent effective therapeutic options for glioma.

In conclusion, the study highlights the pathological role of non-canonical NLRC4 inflammasomes in glioma and proposes several therapeutic strategies based on modulating the inflammatory tumor microenvironment.