EGR2 is a hub-gene in myocardial infarction and aggravates inflammation and apoptosis in hypoxia-induced cardiomyocytes

Bo, Zhixiang; Huang, Shuwen; Li, Li; Chen, Lin; Chen, Ping; Zhu, Bing; Shen, Lin

doi:10.1186/s12872-022-02814-3

Cited by 8 publications

(4 citation statements)

References 41 publications

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“…EGR2, which belongs to the EGR family, has pro-inflammatory and pro-apoptotic effects. EGR2 can directly activate the expression of pro-apoptotic proteins such as BCL2 family and BINP3L, and can also upregulate inflammatory proteins such as IFNG and IL6 50 . Studies have shown that inhibition of EGR2 expression via lncRNA and miRNA can alleviate cardiac apoptosis and protect the heart from ischemic injury 51 , 52 .…”

Section: Discussionmentioning

confidence: 99%

Identification and verification of feature biomarkers associated in heart failure by bioinformatics analysis

Xue

2023

Sci Rep

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Heart failure is the final destination of most cardiovascular diseases, and its complex molecular mechanisms remain largely uncertain. This study aimed to systematically investigate the underlying molecular mechanisms and diagnostic and therapeutic targets of heart failure using bioinformatics. We obtained 8 healthy samples and 8 heart failure samples from GSE8331 and GSE76701. After removing the batch effect, we performed a differential analysis on it and obtained 185 differentially expressed ID. The results of enrichment analysis showed that the molecular mechanisms of heart failure were mostly related to immune, inflammation, and metabolism-related pathways. Immune cell infiltration analysis showed that the degree of infiltration of Tgd cells and Neurons was significantly enriched in heart failure samples, whereas pDCs and NKTs were in healthy tissue samples. We obtained Hub genes including EGR1, EGR2, FOS and FOSB by PPI network analysis. We established a 4-gene diagnostic model with Hub gene, and validated it in GSE21610 and GSE57338, and evaluated the discriminative ability of Hub gene by ROC curve. The 4-gene diagnostic model has an AUC value of 0.775 in GSE21610 and 0.877 in GSE57338. In conclusion, we explored the underlying molecular mechanisms of heart failure and the immune cell infiltration environment of failing myocardium by performing bioinformatic analysis of the GEO dataset. In addition, we identified EGR1, EGR2, FOS and FOSB as potential diagnostic biomarkers and therapeutic targets for heart failure. More importantly, a diagnostic model of heart failure based on these 4 genes was developed, which leads to a new understanding of the pathogenesis of heart failure and may be an interesting target for future in-depth research.

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Section: Discussionmentioning

confidence: 99%

Identification and verification of feature biomarkers associated in heart failure by bioinformatics analysis

Xue

2023

Sci Rep

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“…17 EGR2 is identified to aggravate hypoxia-induced cardiomyocyte inflammation and apoptosis, which is a hub gene in myocardial infarction. 18 In addition, this method has also been implemented in cervical cancer and breast cancer. 19,20 In this study, using bioinformatic analysis, we selected the key gene GNL3L, which may be of vital importance in the progression of COPD.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway

Cai,

Chen,

Zhu

et al. 2023

COPD

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Background: Chronic obstructive pulmonary disease (COPD) is a persistent chronic bronchitis disease, and its potential biomarkers have not been fully expounded. This study aims to explore the role of Guanine nucleotide binding protein like-3-like (GNL3L) in COPD induced by cigarette smoking (CS) in vivo. Methods: Two microarray datasets of COPD were selected to screen differentially expressed genes (DEGs). A protein-protein interaction network was constructed to find hub genes. The COPD model was conducted using CS/LPS-induced mouse and cigarette smoke extract induced human bronchial epithelial cells. The pathological changes of lung tissue in mice were observed by hematoxylin-eosin staining and mean linear intercept. Cell viability was measured by CCK8 assay. Oxidative stress-related indicators, inflammatory factors, and ATM/p53 related-proteins were assessed using ELISA and Western blot. Results: In this study, there were 110 common DEGs identified from the two datasets (GSE5058 and GSE38974). The key gene GNL3L was the optimal indicator to distinguish between samples with COPD and healthy controls. Through the in vivo and in vitro experiments, GNL3L knockdown significantly improved the pathological features of CS/LPS-induced COPD mice, promoted cell viability, inhibited inflammation (IL-1β, IL-8, and TNF-α), oxidative stress (MDA, SOD, and CAT), and ATM/p53 related-proteins (ATM, p53, and p21). Conclusion: GNL3L is a novel biomarker of COPD, and knockdown of GNL3L participates in the progression of COPD by inhibiting ATM/p53 pathway.

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“…Myocardial stroke results in cardiomyocyte cell death due to hypoxia or ischemia caused by an unbalance between the oxygen deposition and requirement in the heart. This ischemia may be caused by an occlusion of the coronary artery with consequent cell death and inflammation [ 94 , 95 , 96 ].…”

Section: Impact Of Lncrnas and Circrnas In Ers And Upr Response On Ca...mentioning

confidence: 99%

LncRNAs and CircRNAs in Endoplasmic Reticulum Stress: A Promising Target for Cardiovascular Disease?

Martinez-Amaro

García-Padilla

Franco

et al. 2023

IJMS

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The endoplasmic reticulum (ER) is a principal subcellular organelle responsible for protein quality control in the secretory pathway, preventing protein misfolding and aggregation. Failure of protein quality control in the ER triggers several molecular mechanisms such as ER-associated degradation (ERAD), the unfolded protein response (UPR) or reticulophagy, which are activated upon ER stress (ERS) to re-establish protein homeostasis by transcriptionally and translationally regulated complex signalling pathways. However, maintenance over time of ERS leads to apoptosis if such stress cannot be alleviated. The presence of abnormal protein aggregates results in loss of cardiomyocyte protein homeostasis, which in turn results in several cardiovascular diseases such as dilated cardiomyopathy (DCM) or myocardial infarction (MI). The influence of a non-coding genome in the maintenance of proper cardiomyocyte homeostasis has been widely proven. To date, the impact of microRNAs in molecular mechanisms orchestrating ER stress response has been widely described. However, the role of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) is just beginning to be addressed given the potential role of these RNA classes as therapeutic molecules. Here, we provide a current state-of-the-art review of the roles of distinct lncRNAs and circRNAs in the modulation of ERS and UPR and their impact in cardiovascular diseases.

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EGR2 is a hub-gene in myocardial infarction and aggravates inflammation and apoptosis in hypoxia-induced cardiomyocytes

Cited by 8 publications

References 41 publications

Identification and verification of feature biomarkers associated in heart failure by bioinformatics analysis

Identification and verification of feature biomarkers associated in heart failure by bioinformatics analysis

Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway

LncRNAs and CircRNAs in Endoplasmic Reticulum Stress: A Promising Target for Cardiovascular Disease?

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