MKRN1 Ubiquitylates p21 to Protect against Intermittent Hypoxia‐Induced Myocardial Apoptosis

Bai, Xue; Yang, Hui; Pu, Jiayuan; Zhao, Yan; Jin, Ying; Yu, Qin

doi:10.1155/2021/9360339

Cited by 9 publications

(7 citation statements)

References 24 publications

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“…Lack of regenerative capacity, cardiomyocytes are replaced by collagen fibers after dying due to inflammation or injury, which eventually leads to myocardial remodeling. Therefore, apoptosis and ageing of the cardiomyocyte plays an essential role in the myocardial disease development, and the inhibition of apoptosis in myocardial ischemic disease shows to mitigate this process [ 21 , 22 ]. In the lncRNA Ftx dysfunction model, we identify multiple proteins involved in apoptosis, evidenced by the upregulation of ITGB1, HMGA2, KRAS and the downregulation of STAT3, RB1, LGALS3.…”

Section: Discussionmentioning

confidence: 99%

Quantitative proteomics analysis revealed the potential role of lncRNA Ftx in cardiomyocytes

Sun

Jiang

et al. 2023

Proteome Sci

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Objective This study aims to decode the proteomic signature of cardiomyocytes in response to lncRNA Ftx knockdown and overexpression via proteomic analysis, and to study the biological role of lncRNA Ftx in cardiomyocytes. Methods The expression level of the lncRNA Ftx in cardiomyocytes cultured in vitro was intervened, and the changes in protein levels in cardiomyocytes were quantitatively detected by liquid chromatography-mass spectrometry. The key molecules and pathways of the lncRNA-Ftx response were further examined by GO, KEGG, and protein interaction analysis. Results A total of 2828 proteins are quantified. With a 1.5-fold change threshold, 32 upregulated proteins and 49 downregulated proteins are identified in the lncRNA Ftx overexpression group, while 67 up-regulated proteins and 54 down-regulated proteins are identified in the lncRNA Ftx knockdown group. Functional clustering analysis of differential genes revealed that the lncRNA Ftx is involved in regulating cardiomyocyte apoptosis and ferroptosis and improving cellular energy metabolism. In addition, Hub genes such as ITGB1, HMGA2, STAT3, GSS, and LPCAT3 are regulated downstream by lncRNA Ftx. Conclusion This study demonstrates that lncRNA Ftx plays a vital role in cardiomyocytes and may be involved in the occurrence and development of various myocardial diseases. It provides a potential target for clinical protection of the myocardium and reversal of myocardial fibrosis.

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Section: Discussionmentioning

confidence: 99%

Quantitative proteomics analysis revealed the potential role of lncRNA Ftx in cardiomyocytes

Sun

Jiang

et al. 2023

Proteome Sci

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“…Makorin Ringinger Protein 1 (MKRN1) is an E3-type ubiquitin ligase. It has been shown that MKRN1 promotes p21 protein ubiquitination and proteasome pathway degradation, thereby preventing intermittent hypoxia (IH)-induced myocardial apoptosis ( 46 ). MKRN1 can disrupt p53 and thus apoptosis through ubiquitination ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Biomarkers Associated With CD8+ T Cells in Coronary Artery Disease and Their Pan-Cancer Analysis

Zhao

Wei

et al. 2022

Front. Immunol.

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PurposeTo identify biomarkers associated with CD8+ T cells in coronary artery disease (CAD) and initially explore their potential role in the tumor immune microenvironment.Materials and MethodsCAD-related datasets GSE12288, GSE34198, and GSE66360, were downloaded from the GEO database. First, GSVA was performed based on the GSE12288 dataset. Then WGCNA analysis was performed to identify the most relevant module and candidate hub gene for CD8+ T cells, followed by GO and KEGG analysis of this module. Secondly, the relationship between candidate hub genes and CD8+ T cells was verified using GSE34198 and GSE66360, which led to the identification of hub genes. The relationship of hub genes with CD8+ T cells in cancer was analyzed using the TIMER database. Methylation analysis of hub genes was performed using the DiseaseMeth database. CAD, pan-cancer, pan-cell lines, and pan-normal tissues, correlations between hub genes. In addition, potential drugs and TFs associated with hub genes were predicted, and the ceRNA network was constructed. Finally, GSEA was performed separately for hub genes.ResultsCAD was shown to be associated with immune response by GSVA analysis. WGCNA identified the blue module as most related to CD8+ T cells and identified nine candidate hub genes. The relevance of CAD to immunity was further confirmed by GO and KEGG analysis of the module. Two additional datasets validated and identified three hub genes (FBXO7, RAD23A, and MKRN1) that significantly correlated with CD8+ T cells. In addition, we found that hub genes were positively associated with CD8+ T cells in TGCT, THCA, and KICH cancers by our analysis. Moreover, the hub gene was differentially methylated. We also analyzed the correlation between hub genes in CAD, different cancers, different cell lines, and different normal tissues. The results of all the analyses showed a positive correlation between them. Finally, we successfully constructed hub gene-associated TF-gene and ceRNA networks and predicted 11 drugs associated with hub genes. GSEA suggests that hub genes are related to multiple immune response processes.ConclusionFBXO7, RAD23A, and MKRN1 are significantly associated with CD8+ T cells in CAD and multiple cancers and may act through immune responses in CAD and cancer.

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“…MKRN1, an E3 ubiquitin ligase, plays a significant role in regulating disorders through the ubiquitination of substrate proteins. Bai et al found that MKRN1 could promote p21 protein ubiquitination and the proteasome pathway degradation to negatively regulate p21 expression, thereby preventing intermittent hypoxia-induced myocardial apoptosis [ 24 ]. Kotla et al found that MKRN1 expression was inhibited by TERF2IP S205 phosphorylation and it promoted endothelial cell activation and senescence, contributing to the development of atherogenesis [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Construction of a circRNA-miRNA-mRNA Regulatory Network for Coronary Artery Disease by Bioinformatics Analysis

Zhang

Qian

Wang

et al. 2022

Cardiology Research and Practice

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Background. Circular RNAs (circRNAs) were known to be related to the pathogenesis of many diseases through competing endogenous RNA (ceRNA) regulatory mechanisms. However, the function of circRNA in coronary artery disease (CAD) remains unclear. In this study, we aim to construct a circRNA-related competing endogenous RNA (ceRNA) network in CAD. Methods. The gene expression profiles of CAD were obtained from Gene Expression Omnibus datasets. Bioinformatics analysis was performed to construct a ceRNA regulatory network, from which the hub genes involved were identified through protein-protein interaction (PPI) networks leading to the identification of the circRNA-miRNA-hub gene subnetwork. In addition, function enrichment analysis was performed to detect the potential biological mechanism in which circRNA might be involved. Results. A total of 115 DEcircRNAs (differentially expressed circRNAs), 17 DEmiRNAs (differentially expressed microRNAs), and 790 DEmRNAs (differentially expressed mRNAs) were identified between CAD and control groups from microarray datasets. Functional enrichment analysis showed that DEmRNAs were significantly involved in inflammation-related pathways and ubiquitin-protein ligase binding. After identifying 20 DEcircRNA-DEmiRNA pairs and 561 DEmiRNA-DEmRNA pairs, we obtained a circRNA-miRNA-mRNA regulatory network. PPI network analysis showed that eight hub genes were closely related to CAD, leading to the identification of a circRNA-miRNA-hub gene subnetwork consisting of nine circRNAs (hsa_circ_0020275, hsa_circ_0020387, hsa_circ_0020417, hsa_circ_0045512, hsa_circ_0047336, hsa_circ_0069094, hsa_circ_0071326, hsa_circ_0071330, and hsa_circ_0085340), four miRNAs (hsa-miR-136-5p, hsa-miR-376c-3p, hsa-miR-411-5p, and hsa-miR-654-5p), and eight mRNAs (MKRN1, UBE2H, UBE2W, UBE2D1, UBE2F, BE2J1, ZNRF1, and SIAH2). In addition, we discovered these hub genes were enriched in the ubiquitin-mediated proteolysis pathway, suggesting circRNAs may be involved in the pathogenesis of CAD through this pathway. Conclusions. This study may deepen our understanding of the potential role of circRNA-miRNA-mRNA regulation network in CAD and suggest novel diagnostic biomarkers and therapeutic targets for CAD.

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MKRN1 Ubiquitylates p21 to Protect against Intermittent Hypoxia‐Induced Myocardial Apoptosis

Cited by 9 publications

References 24 publications

Quantitative proteomics analysis revealed the potential role of lncRNA Ftx in cardiomyocytes

Quantitative proteomics analysis revealed the potential role of lncRNA Ftx in cardiomyocytes

Identification of Biomarkers Associated With CD8+ T Cells in Coronary Artery Disease and Their Pan-Cancer Analysis

Construction of a circRNA-miRNA-mRNA Regulatory Network for Coronary Artery Disease by Bioinformatics Analysis

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