Neutrophil Extracellular Traps (NETs) Promote Non-Small Cell Lung Cancer Metastasis by Suppressing lncRNA MIR503HG to Activate the NF-κB/NLRP3 Inflammasome Pathway

Wang, Yong; Liu, Fen; Chen, Lin; Chen, Fang; Li, Shuangyan; Yuan, Shangkun; Qian, Xiaoying; Yin, Yan; Yu, Biao; Fu, Biqi; Zhang, Xinwei; Li, Yong

doi:10.3389/fimmu.2022.867516

Cited by 48 publications

(28 citation statements)

References 70 publications

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“…Active caspase-1 cleaves pro-IL-1b into mature and biologically active IL-1b, which is a potent proinflammatory mediator (Moretti and Blander, 2021). PMA-induced NETs have been shown to upregulate NLRP3 and IL-1b levels via a NF-kB signaling pathway in the tumour microenvironment in vitro (Wang et al, 2022). In this present study, it was confirmed that NETs further up-regulated NLRP3 and IL-1b expression in a high glucose inflammatory condition.…”

Section: Discussionsupporting

confidence: 81%

Excessive neutrophil extracellular trap formation induced by Porphyromonas gingivalis lipopolysaccharide exacerbates inflammatory responses in high glucose microenvironment

Tong

Yue²,

Fu³

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionNeutrophil extracellular trap (NET) is a novel defense strategy of neutrophils and found to be induced by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) or high glucose. The aim of this study was to investigate the roles and mechanisms of NET formation in high glucose inflammatory microenvironment.MethodsNETs induced by 1 μg/ml P. gingivalis LPS and/or 25 mM glucose were visualized using a fluorescence microscopy and the levels of extracellular DNA were determined by a microplate reader. The bactericidal efficiency of NETs was assessed by quantifying the survival P. gingivalis in neutrophils. The levels of NLRP3 and IL-1β in THP-1 derived-macrophages, and the expressions of p-PKC βII, p-MEK1/2, p-ERK1/2, ORAI1 and ORAI2 in neutrophils were detected by Western blot. Moreover, levels of intracellular Ca2+ and reactive oxygen species (ROS) in neutrophils were explored by flow cytometry.ResultsP. gingivalis LPS enhanced the formation of NETs and increased the levels of extracellular DNA in high glucose microenvironment (p < 0.05). Compared with normal glucose inflammatory microenvironment, quantities of extra- and intracellular viable P. gingivalis in neutrophils exposed to NETs induced in high glucose inflammatory one were increased (p < 0.05) and the expressions of NLRP3 and IL-1β were dramatically increased in macrophages co-cultured with NETs from high glucose inflammatory microenvironment (p < 0.05). In addition, levels of ROS, intracellular Ca2+, p-PKC βII, p-MEK1/2, p-ERK1/2, ORAI1 and ORAI2 were increased in neutrophils stimulated with both high glucose and P. gingivalis LPS compared with the single stimulus groups (p < 0.05).DiscussionIn high glucose inflammatory microenvironment, formation of NETs was enhanced via oxidative stress, which failed to reverse the decreased bactericidal capacity in high glucose microenvironment, and instead aggravated the subsequent inflammatory responses.

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Section: Discussionsupporting

confidence: 81%

Excessive neutrophil extracellular trap formation induced by Porphyromonas gingivalis lipopolysaccharide exacerbates inflammatory responses in high glucose microenvironment

Tong

Yue²,

Fu³

et al. 2023

Front. Cell. Infect. Microbiol.

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“…Functionally, NETs function as a physical barrier to shield tumor cells from interactions with neighboring anti-tumor immune cells such as NK cells and CD8 + T cells in the tumor immune microenvironment (TME), affecting the tumor immune landscape and tumor response to immunotherapy ( Ireland and Oliver, 2020 ; Teijeira et al, 2020 ). LncRNAs, as particular type of non-coding RNAs, have been reported to mediate NETs-induced cancer cell metastasis in the TME ( Wang et al, 2022 ). Therefore, the exploration of the relevance of the model based on NETs-related lncRNAs and the immune microenvironment of BC patients is essential.…”

Section: Discussionmentioning

confidence: 99%

“…The long non-coding RNAs (lncRNAs), non-coding RNA longer than 200 nucleotides, do not directly participate in protein coding in cells, but are engaged in vital biological regulatory processes, including transcriptional regulation, mRNA processing regulation and mRNA post-transcriptional regulation ( Yang et al, 2022 ). Recent finding indicated a role of lncRNA in regulating NETs in lung cancer ( Wang et al, 2022 ). However, the lncRNAs associated with NETs in BC are less studied, and most lncRNAs regulating NETs have not been determined.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil extracellular traps (NETs)-related lncRNAs signature for predicting prognosis and the immune microenvironment in breast cancer

Jiang

Wang

Chen

et al. 2023

Front. Cell Dev. Biol.

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Background: Neutrophil extracellular traps (NETs) are closely associated to tumorigenesis and development. However, the relationship between NETs-related long non-coding RNAs (lncRNAs) and the characteristics of breast tumor remains an enigma. This study aimed to explore the clinical prognostic value of NETs-related lncRNAs, their correlation with the tumor microenvironment (TME) and their predictive ability of drug sensitivity in patients with breast cancer (BC).Methods: The expression profiles of RNA-sequencing and relevant clinical data of BC patients were extracted from TCGA database. The co-expression network analysis, univariable, least absolute shrinkage and selection operator (LASSO) and multivariable Cox algorithms were employed to construct the NETs-related lncRNAs signature. A nomogram was established and validated to explore the clinical application. Furthermore, the immune microenvironment and drug sensitivity for BC with different prognostic risks were explored. Finally, the expression pattern of lncRNAs was validated using qRT-PCR in BC tissues and their adjacent non-cancerous tissues.Results: Based on NETs-related lncRNAs, a prognostic risk model consisted of 10 lncRNAs (SFTA1P, ACTA2-AS1, AC004816.2, AC000067.1, LINC01235, LINC01010, AL133467.1, AC092919.1, AL591468.1, and MIR200CHG) was established. The Kaplan-Meier analysis showed that the overall survival (OS) was significantly better in low-risk BC patients than in high-risk BC patients (Ptraining cohort < 0.001, Pvalidation cohort = 0.009). The nomogram also showed good predictive accuracy for OS of BC individuals in both training and validation cohorts. The function enrichment analysis revealed that high-risk group was mainly enriched in immune-related functions and pathways, and the tumor mutation burden in this group was markedly higher than that in the low-risk group (p = 0.022). Moreover, significant differences were observed in immune cells, immune functions and immune checkpoint genes among BC patients at different risks (p < 0.05). The response to chemotherapeutic agents and immunotherapy were also closely related with the expression of NETs-related lncRNAs (p < 0.001). The expression of lncRNAs from experimental validation were generally consistent with the bioinformatics analysis results.Conclusion: Our study provided a novel prognostic model for BC and yielded strong scientific rationale for individualized treatment strategies, elucidating immunotherapy in BC patients.

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“…While lncRNA-BACE1-AS is an immune-related factor in the tumorigenesis of melamona, its expression levels are negatively correlated with the neutrophil content ( 108 ). Neutrophil extracellular traps (NETs) generated in the tumor microenvironment promote the EMT process and metastasis by promoting the expression of lncRNA-MIR503HG and activating the downstream NF-κB/NLRP3 signaling pathway ( 109 ). Therefore, lncRNAs play an important role in the regulation of the immune microenvironment, thus affecting tumor progression.…”

Section: Lncrnas In the Immune Microenvironmentmentioning

confidence: 99%

The role of lncRNAs in the tumor microenvironment and immunotherapy of melanoma

Zhou

Cen

et al. 2022

Front. Immunol.

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Melanoma is one of the most lethal tumors with highly aggressive and metastatic properties. Although immunotherapy and targeted therapy have certain therapeutic effects in melanoma, a significant proportion of patients still have drug resistance after treatment. Recent studies have shown that long noncoding RNAs (lncRNAs) are widely recognized as regulatory factors in cancer. They can regulate numerous cellular processes, including cell proliferation, metastasis, epithelial-mesenchymal transition (EMT) progression and the immune microenvironment. The role of lncRNAs in malignant tumors has received much attention, whereas the relationship between lncRNAs and melanoma requires further investigation. Our review summarizes tumor suppressive and oncogenic lncRNAs closely related to the occurrence and development of melanoma. We summarize the role of lncRNAs in the immune microenvironment, immunotherapy and targeted therapy to provide new targets and therapeutic methods for clinical treatment.

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Neutrophil Extracellular Traps (NETs) Promote Non-Small Cell Lung Cancer Metastasis by Suppressing lncRNA MIR503HG to Activate the NF-κB/NLRP3 Inflammasome Pathway

Cited by 48 publications

References 70 publications

Excessive neutrophil extracellular trap formation induced by Porphyromonas gingivalis lipopolysaccharide exacerbates inflammatory responses in high glucose microenvironment

Excessive neutrophil extracellular trap formation induced by Porphyromonas gingivalis lipopolysaccharide exacerbates inflammatory responses in high glucose microenvironment

Neutrophil extracellular traps (NETs)-related lncRNAs signature for predicting prognosis and the immune microenvironment in breast cancer

The role of lncRNAs in the tumor microenvironment and immunotherapy of melanoma

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