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Whole transcriptome sequencing indicated the Anti-tumor immunity of NLRP3 in breast cancer.

Authors :
Qian, Da
Qiu, Jie
Xu, Yadan
Hong, Weimin
He, Chaoqi
Guan, Dandan
Zheng, Qinghui
Liu, Xiaozhen
Wu, Chaoshen
Meng, Xuli
Tang, Hongchao
Source :
Genomics. Sep2024, Vol. 116 Issue 5, pN.PAG-N.PAG. 1p.
Publication Year :
2024

Abstract

Breast cancer (BC) is a prevalent cancer of the female reproductive system and a major contributor to cancer-related mortality. The activation of NLRP3, a key inflammasome, has been extensively associated with tumor-related molecular and cellular processes; however, the regulatory mechanisms and specific role of NLRP3 in breast cancer remain incompletely elucidated. This study aimed to evaluate the molecular mechanisms of NLRP3-related genes in BC. Utilizing bioinformatics methods, the present research analyzed the TCGA-BRCA dataset, which included four groups of transcriptome sequencing data as follows, normal (WT), NLRP3 knockout (KO), non-knockout-BRCA (BC-WT), and NLRP3-knockout-BRCA (BC-KO). Results indicated that NLRP3 was significantly down-regulated in TCGA-BRCA. Key module genes were mainly enriched in leukocyte cell-cell adhesion and cytokine-cytokine receptor interaction. Moreover, correlation analysis showed that NLRP3 was positively associated with cancer-associated fibroblasts and negatively associated with CD4+ Th1 T-cells. In addition, the DEGs1 and DEGs2 overlapping indicated 505 feature genes, with Chac1 (negative) and Ugt8a (positive) had the strongest correlation with differential immune cells (class-switched memory B cells). Pathway intersection revealed 13 co-KEGG pathways. The BC-KO group indicated markedly reduced levels of four genes (Ccl19, Ccl20, Ccl21a, and H2-Oa) and increased levels of two genes (Il2ra and H2-Ob). This study delved into the role of NLRP3 in BC, exploring its regulatory mechanisms and the impact gene knockout. Bioinformatics approaches identified NLRP3-associated genes, their enriched pathways, and interactions within the tumor microenvironment (TME), providing novel insights into NLRP3 function, TME dynamics, and potential targets for BC prevention and treatment. • NLRP3 plays a significant role in breast cancer (BC). • TCGA-BRCA and four transcriptome sequencing data revealed the role of NLRP3 in BC. • NLRP3 may affect the development or function of Class-switched B-memory cells. • Six NLRP3-related genes were identified participating in the progression of BC. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
08887543
Volume :
116
Issue :
5
Database :
Academic Search Index
Journal :
Genomics
Publication Type :
Academic Journal
Accession number :
180115614
Full Text :
https://doi.org/10.1016/j.ygeno.2024.110930