Knockdown of EDA2R alleviates hyperoxia-induced lung epithelial cell injury by inhibiting NF-κB pathway

Nan, Jun; Jia, Yunyi; Yang, Fang; Wen, Du

doi:10.15586/aei.v50i5.670

Cited by 7 publications

(6 citation statements)

References 20 publications

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“…For instance, EDA2R has been implicated in isoform EDA-A2-induced apoptosis of hair follicle cells [6] and osteosarcoma cells [43]. Furthermore, silencing of EDA2R enhanced the viability and reduced the apoptosis of hyperoxia-induced murine lung epithelial cells [12]. The present findings suggested that EDA2R knockdown increased cell viability and suppressed H/R-induced cardiomyocyte apoptosis.…”

Section: Discussionsupporting

confidence: 56%

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Ectodysplasin-A2 receptor (EDA2R) knockdown alleviates myocardial ischemia/reperfusion injury through inhibiting the activation of the NF-κB signaling pathway

Guan,

Yang,

Wang

et al. 2024

Exp. Anim.

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Ischemia/reperfusion (I/R) is a pathological process that occurs in numerous organs and is often associated with severe cellular damage and death.Ectodysplasin-A2 receptor (EDA2R) is a member of the TNF receptor family that has anti-inflammatory and antioxidant effects. However, to the best of our knowledge, its role in the progression of myocardial I/R injury remains unclear. The present study aimed to investigate the role of EDA2R during myocardial I/R injury and the molecular mechanisms involved. In vitro, dexmedetomidine (DEX) exhibited a protective effect on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and downregulated EDA2R expression. Subsequently, EDA2R silencing enhanced cell viability and reduced the apoptosis of cardiomyocytes. Furthermore, knockdown of EDA2R led to an elevated mitochondrial membrane potential (MMP), repressed the release of Cytochrome C and upregulated Bcl-2 expression. EDA2R knockdown also resulted in downregulated expression of Bax, and decreased activity of Caspase-3 and Caspase-9 in cardiomyocytes, reversing the effects of H/R on mitochondria-mediated apoptosis. 2 In addition, knockdown of EDA2R suppressed H/R-induced oxidative stress. Mechanistically, EDA2R knockdown inactivated the NF-κB signaling pathway. Additionally, downregulation of EDA2R weakened myocardial I/R injury in mice, as reflected by improved left ventricular function and reduced infarct size, as well as suppressed apoptosis and oxidative stress. Additionally, EDA2R knockdown repressed the activation of NF-κB signal in vivo. Collectively, knockdown of EDA2R exerted anti-apoptotic and antioxidant effects against I/R injury in vivo and in vitro by suppressing the NF-κB signaling pathway.

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Section: Discussionsupporting

confidence: 56%

“…Furthermore, knockdown of EDA2R reduces cell apoptosis, and exerts antiinflammatory and antioxidant effects against hyperoxia-induced injury in lung epithelial cells [12]. These reports indicated that EDA2R may be involved in regulating cell apoptosis and oxidative stress.…”

Section: Introductionmentioning

confidence: 86%

Ectodysplasin-A2 receptor (EDA2R) knockdown alleviates myocardial ischemia/reperfusion injury through inhibiting the activation of the NF-κB signaling pathway

Guan,

Yang,

Wang

et al. 2024

Exp. Anim.

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“…XEDAR can activate typical nuclear factor-κB (NF-κB) pathways and atypical NF-κB signaling pathways by direct interaction with TRAF3 and TRAF6 ( 37 ). Some researchers have found that EDA2R can reduce the inflammatory effect of cell injury through the NF-κB pathway ( 38 ). The atypical NF-κB signal induced by XEDAR involves NF-κB inducing kinase (NIK) and inhibitor of kappa B kinase α (IKKα) and is negatively regulated by TRAF3, cIAP, and A20 ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Landscape of costimulatory molecule signature in breast cancer and its prognostic significance

Kang¹,

Yun²,

Shi³

et al. 2023

Ann Transl Med

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Background Breast cancer (BRCA) is the most common malignant tumor in the world. Because of its substantial heterogeneity, its clinical treatment is faced with various problems. Only a small number of patients can benefit from the treatment of immune checkpoint inhibitor (ICI). Costimulatory molecule signature (CMS) plays an essential role in T cell activation and antitumor immune response. Previous studies found that CMS is associated with prognosis-related immune response markers, suggesting that CMS may be a potential therapeutic target. However, the research on their function in BRCA subtype is still inadequate. Our study aims to analyze CMS in BRCA and establish an effective prognostic model. Methods We extracted 1,222 messenger RNA (mRNA) samples of 1,110 patients registered in the BRCA cohort of The Cancer Genome Atlas (TCGA), including 1,109 tumor tissue mRNA samples and 113 standard tissue samples for model construction and verification. The prognostic significance was determined by least absolute shrinkage and selection operator (LASSO)-Cox proportional hazard regression, which showed that the overall survival (OS) of the high-risk group was shorter than that of the low group (P<0.01). Results Although the CMS prognostic model can predict the prognosis well, the receiver operating characteristic (ROC) prediction results were unsatisfactory. The reason for this may be the heteromorphism of BRCA, so we divided the cases into four subtypes according to the PAM50 (PAM50Call_RNAseq) in clinical information. The same method was used to construct the model in the four subtypes and verify the effect of each subtype prognostic model. Conclusions The results showed that the submodels constructed in this study can be used to evaluate the prognosis of each subtype.

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“…Knockdown of PHLDA2 similarly inhibited pancreatic cancer invasion and migration [50] . By encouraging the enrichment of sarcoma fusions on the EDA2R promoter, which results in EDA2R overexpression and activation of apoptotic signaling, IrcHIPK3 indicated that the circHIPK3 / FUS / EDA2R axis is a therapeutic target for the development of diabetic nephropathy [51] .Jia et al [52] showed through their research that blocking the NF-B pathway by silencing EDA2R increased hyperoxia-induced lung epithelial cell viability, decreased apoptosis, and ultimately mitigated hyperoxia-induced lung epithelial cell injury. By regulating the PI3K/Akt signaling pathway, LAMB3 in pancreatic cancer can cause cell cycle arrest and death in the cancer cells, affecting their proliferative, invasive, and metastatic features, as demonstrated by Zhu, Song et al [53,54] .…”

Section: Discussionmentioning

confidence: 99%

Anoikis-related Genes in Breast Cancer Patients: Reliable Biomarker of Prognosis

Tang

Rong

Zhang

et al. 2023

Preprint

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Background Brest cancer (BC) is the most common cancer in women and the second most frequent type of newly diagnosed cancer worldwide. Second, anoikis, a specific programmed death brought on by a cell's lack of contact with the extracellular matrix, is crucial for the spread of cancer. The impact of anoikis on BC patients' prognoses, however, is still unknown. Method Via the TCGA and GEO databases, we gathered patient transcriptome and clinical group data for this investigation. The classification of subtypes A and B, subtype survival analysis, and pathway analysis were performed using anoikis-related genes (ARGs). the least absolute shrinkage and selection operator (LASSO), multivariate Cox regression analysis, and tumor microenvironment were used to evaluate the immune microenvironment (TME). Ultimately, ten ARGs relevant to prognosis were collected, and prognostic models were created. In order to characterize the correlation of ARGS, we also performed single cell data analysis. Finally, we used real-time polymerase chain reaction (RT-PCR) to analyze the associations between the 10 prognostic ARGS and BC cells. Results By using Kaplan-Meier (KM) and receiver operating characteristic (ROC) curve analyses, we were able to identify ten ARGS (YAP1, PIK3R1, BAK1, PHLDA2, EDA2R, LAMB3, CD24, SLC2A1, CDC25C, and SLC39A6) as BC prognosis-related ARGS. These characteristics of the high-risk group of ARGS were linked to a poor prognosis in BC patients. KEGG functional analysis revealed that the immunological state of these high- and low-risk groups was different. By building a carcinogenesis model of risk score, risk score was found to be an independent prognostic factor. YAP1, PIK3R1, BAK1, PHLDA2, EDA2R, CD24, SLC2A1, and CDC25C were all strongly expressed in BC cells, according to the results of the RT-PCR analysis. were poorly expressed in SLC39A6 and LAMB3BC cells, but were strongly expressed in BC cells. The outcomes agreed with our earlier analysis of differential expression. Conclusion ARGS markers can be used as BC biomarkers for risk stratification and survival prediction in BC patients. Besides, ARGs can be used as stratification factors for individualized and precise treatment of BC patients.

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Knockdown of EDA2R alleviates hyperoxia-induced lung epithelial cell injury by inhibiting NF-κB pathway

Cited by 7 publications

References 20 publications

Ectodysplasin-A2 receptor (EDA2R) knockdown alleviates myocardial ischemia/reperfusion injury through inhibiting the activation of the NF-κB signaling pathway

Ectodysplasin-A2 receptor (EDA2R) knockdown alleviates myocardial ischemia/reperfusion injury through inhibiting the activation of the NF-κB signaling pathway

Landscape of costimulatory molecule signature in breast cancer and its prognostic significance

Anoikis-related Genes in Breast Cancer Patients: Reliable Biomarker of Prognosis

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