NR4A1 suppresses pyroptosis by transcriptionally inhibiting NLRP3 and IL‐1β and co‐localizing with NLRP3 in trans‐Golgi to alleviate pathogenic bacteria‐induced colitis

Deng, Zhao; Yang, Zhipeng; Cui, Chenbin; Wei, Hongkui; Wang, Lijia; Tian, Dean; Xiao, Fang; Peng, Jian

doi:10.1002/ctm2.639

Cited by 8 publications

(5 citation statements)

References 10 publications

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“…NLRP12 inhibits the inflammatory response by downregulating NF‐κB and ERK activation, 59 and its deficiency increases the risk of CAC. In addition, Deng et al reported that NR4A1 inhibited NLRP3 inflammasome and thus reduces inflammation and colitis 60 . The protective effect of these inflammasomes may be further evaluated for the treatment of CAC in the future.…”

Section: Pyroptosis In Digestive Tract Tumorsmentioning

confidence: 99%

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Recent updates on pyroptosis in tumors of the digestive tract

Wang,

Shang,

et al. 2023

J of Digest Diseases

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Pyroptosis is an inflammasome‐dependent form of programmed cell death that is mediated by caspase‐1,caspase‐4/5/11 and the gasdermin protein family. It is characterized by the rupture of cell membranes, the release of cell contents and interleukins, the associated inflammatory reaction and immune system activation. Recent studies have suggested that pyroptosis plays a role in the development of digestive tract tumors，both impeding tumor generation and progression, as well as providing a favorable microenvironment for tumor growth. This review outlines the current knowledge regarding the implications of pyroptosis in gastrointestinal cancers with a focus on providing insights into their pathogenesis and potential treatments.This article is protected by copyright. All rights reserved.

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Section: Pyroptosis In Digestive Tract Tumorsmentioning

confidence: 99%

“…In addition, Deng et al reported that NR4A1 inhibited NLRP3 inflammasome and thus reduces inflammation and colitis. 60 The protective effect of these inflammasomes may be further evaluated for the treatment of CAC in the future.…”

Section: Colitis-associated Colorectal Cancer (Cac)mentioning

confidence: 99%

Recent updates on pyroptosis in tumors of the digestive tract

Wang,

Shang,

et al. 2023

J of Digest Diseases

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“…One of the most critical components of the inflammatory response is the inflammasome, and the dysregulation of NLRP3 inflammasomes is associated with IBD [59]. Deng et al [131] found that NR4A1 inhibits the NLRP3 inflammasome to prevent inflammation and protect against C. rodentium-induced colitis. Nek7 is an essential component of NLRP3 inflammasome activation and coordinates with NLRP3 to regulate pyroptosis in IBD by activating NF-κB signaling [132].…”

Section: Necroptosis and Intestinal Injurymentioning

confidence: 99%

The Induction Mechanism of Ferroptosis, Necroptosis, and Pyroptosis in Inflammatory Bowel Disease, Colorectal Cancer, and Intestinal Injury

et al. 2023

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Cell death includes programmed and nonprogrammed cell death. The former mainly includes ferroptosis, necroptosis, pyroptosis, autophagy, and apoptosis, while the latter refers to necrosis. Accumulating evidence shows that ferroptosis, necroptosis, and pyroptosis play essential regulatory roles in the development of intestinal diseases. In recent years, the incidence of inflammatory bowel disease (IBD), colorectal cancer (CRC), and intestinal injury induced by intestinal ischemia–reperfusion (I/R), sepsis, and radiation have gradually increased, posing a significant threat to human health. The advancement in targeted therapies for intestinal diseases based on ferroptosis, necroptosis, and pyroptosis provides new strategies for treating intestinal diseases. Herein, we review ferroptosis, necroptosis, and pyroptosis with respect to intestinal disease regulation and highlight the underlying molecular mechanisms for potential therapeutic applications.

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“…PANoptosis is an emerging concept that highlights the crosstalk and coordination between these three pathways 10,11 . It is able to eliminate intracellular pathogens and maintain homeostasis in the body 12,13 . Originally proposed in 2019, although scorch death, apoptosis and necroptosis have been described as distinct and independent pathways throughout the history of research, there is growing evidence of extensive interactions between these programmed cell death pathways.…”

Section: Introductionmentioning

confidence: 99%

“…10,11 It is able to eliminate intracellular pathogens and maintain homeostasis in the body. 12,13 Originally proposed in 2019, although scorch death, apoptosis and necroptosis have been described as distinct and independent pathways throughout the history of research, there is growing evidence of extensive interactions between these programmed cell death pathways. The interactions between each pair of pathways have now been clarified (apoptosis vs. apoptosis, apoptosis vs. necroptosis, and apoptosis vs. necroptosis), and a growing number of studies have mechanistically defined the interactions between the three pathways.…”

mentioning

confidence: 99%

Machine learning reveals PANoptosis as a potential reporter and prognostic revealer of tumour microenvironment in lung adenocarcinoma

Han,

Danzeng,

et al. 2023

The Journal of Gene Medicine

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Lung adenocarcinoma (LUAD), a prominent lung cancer subtype, has an underexplored relationship with PANoptosis, a recently discovered mode of tumour cell death. This study incorporated iron death, copper death, scorch death, necrotizing apoptosis and bisulfide death into a pan‐death gene set (PANoptosis) and conducted single‐cell analysis of scRNA‐seq data from 11 LUAD samples. Differentially expressed genes were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. Univariate COX regression and least absolute shrinkage and selection operator (LASSO) regression were used to screen PANoptosis key genes for constructing an LUAD risk model. The model’s prognostic performance was evaluated using survival curves, risk scores and validation in the Gene Expression Omnibus database. The study also explored the correlation between risk scores, tumour biological function, immunotherapy, drug sensitivity and immune infiltration. The SMS gene in the PANoptosis model was silenced in two LUAD cell lines for cellular validation. Single‐cell analysis revealed eight major cell types and several PANoptosis genes significantly associated with LUAD survival. The risk model demonstrated strong prognostic performance and association with immune infiltration, suggesting PANoptosis involvement in LUAD tumour immunity. Cellular validation further supported these findings. The PANoptosis key risk genes are believed to be closely related to the tumour microenvironment and immune regulation of LUAD, potentially providing valuable insights for early diagnosis and clinical treatment, and broader applications in other tumours and complex diseases.

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NR4A1 suppresses pyroptosis by transcriptionally inhibiting NLRP3 and IL‐1β and co‐localizing with NLRP3 in trans‐Golgi to alleviate pathogenic bacteria‐induced colitis

Cited by 8 publications

References 10 publications

Recent updates on pyroptosis in tumors of the digestive tract

Recent updates on pyroptosis in tumors of the digestive tract

The Induction Mechanism of Ferroptosis, Necroptosis, and Pyroptosis in Inflammatory Bowel Disease, Colorectal Cancer, and Intestinal Injury

Machine learning reveals PANoptosis as a potential reporter and prognostic revealer of tumour microenvironment in lung adenocarcinoma

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