CircUbe3a from M2 macrophage-derived small extracellular vesicles mediates myocardial fibrosis after acute myocardial infarction

Wang, Yan; Li, Chaofu; Zhao, Ranzun; Qiu, Zhimei; Shen, Changyin; Wang, Zhenglong; Liu, Weiwei; Zhang, Wei; Ge, Junbo; Shi, Bei

doi:10.7150/thno.52843

Cited by 86 publications

(75 citation statements)

References 49 publications

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“…Moreover, circUbe3a, which is transported into CFs from M2 macrophages (M2Ms) through small extracellular vesicles (SEVs), was also verified to sponge miR-138-5p and indirectly upregulate the expression of the target protein RhoC to accelerate proliferation, migration, and myofibroblastic transformation of CFs. 133 In contrast, circNFIB alleviates fibroblast proliferation, and its expression is significantly decreased in post-MI mouse hearts and TGF-β-treated primary adult CFs. 134 Mechanistically, circNFIB can directly sponge miR-433 and consequently promote the expression of target genes such as AZIN1 and JNK1 and inhibit their downstream signaling pathways, including the p38, ERK, and Smad3 pathways.…”

Section: Circrnas and Cardiac Remodeling After MImentioning

confidence: 97%

“… 120 During infarct healing, circHelz can exert anti-inflammatory effects, 122 circCDYL and circFASTKD1 are likely to contribute to proliferation and proangiogensis, 123 , 127 and circUbe3a can exert anti-fibrotic effects. 133 Moreover, circRNA_000203, circNFIB, and circ_LAS1L can have anti-fibrotic effects. 131 , 134 , 135 …”

Section: Circrna-based Approaches As Potential Therapeutic Strategies For MImentioning

confidence: 99%

“…The circRNA-miRNA interaction can be predicted with the help of Arraystar’s proprietary miRNA target-prediction software Interaction. 133 , 183 In addition, the RNA pull-down assay and RNA immunoprecipitation (RIP) assay followed by circRNA sequencing are practical strategies for predicting circRNA-protein interactions. 184 …”

Section: Strategies For Measuring Circrna Levels In the Context Of MImentioning

confidence: 99%

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Emerging roles of circRNAs in the pathological process of myocardial infarction

Wen

Hui

Wang

et al. 2021

Molecular Therapy - Nucleic Acids

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Myocardial infarction (MI) is defined as cardiomyocyte death in a clinical context consistent with ischemic insult. MI remains one of the leading causes of morbidity and mortality worldwide. Although there are a number of effective clinical methods for the diagnosis and treatment of MI, further investigation of novel biomarkers and molecular therapeutic targets is required. Circular RNAs (circRNAs), novel non-coding RNAs, have been reported to function mainly by acting as microRNA (miRNA) sponges or binding to RNA-binding proteins (RBPs). The circRNA-miRNA-mRNA (protein) regulatory pathway regulates gene expression and affects the pathological mechanisms of various diseases. Undoubtedly, a more comprehensive understanding of the relationship between MI and circRNA will lay the foundation for the development of circRNA-based diagnostic and therapeutic strategies for MI. Therefore, this review summarizes the pathophysiological process of MI and various approaches to measure circRNA levels in MI patients, tissues, and cells; highlights the significance of circRNAs in the regulation MI pathogenesis and development; and provides potential clinical insight for the diagnosis, prognosis, and treatment of MI.

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Section: Circrnas and Cardiac Remodeling After MImentioning

confidence: 97%

Section: Circrna-based Approaches As Potential Therapeutic Strategies For MImentioning

confidence: 99%

Section: Strategies For Measuring Circrna Levels In the Context Of MImentioning

confidence: 99%

See 1 more Smart Citation

Emerging roles of circRNAs in the pathological process of myocardial infarction

Wen

Hui

Wang

et al. 2021

Molecular Therapy - Nucleic Acids

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“…In addition, SiO 2 induces macrophage activation through the circHECTD1/HECTD1 pathway and circZC3H4 RNA and ZC3H4 protein in the process of pulmonary fibrosis ( 120 , 121 ). In addition, circRNA HIPK3 and circUbe3a can activate macrophages, while the latter participates in the process of myocardial fibrosis ( 122 , 123 ).…”

Section: Roles Of Circrnas In Immune-related Diseasesmentioning

confidence: 99%

Past, Present and Future: The Relationship Between Circular RNA and Immunity

Huang

et al. 2022

Front. Immunol.

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The immune system has evolved since the birth of humans. However, immune-related diseases have not yet been overcome due to the lack of expected indicators and targeting specificity of current medical technology, subjecting patients to very uncomfortable physical and mental experiences and high medical costs. Therefore, the requirements for treatments with higher specificity and indicative ability are raised. Fortunately, the discovery of and continuous research investigating circular RNAs (circRNAs) represent a promising method among numerous methods. Although circRNAs wear regarded as metabolic wastes when discovered, as a type of noncoding RNA (ncRNA) with a ring structure and wide distribution range in the human body, circRNAs shine brilliantly in medical research by virtue of their special nature and structure-determined functions, such as high stability, wide distribution, high detection sensitivity, acceptable reproducibility and individual differences. Based on research investigating the role of circRNAs in immunity, we systematically discuss the hotspots of the roles of circRNAs in immune-related diseases, including expression profile analyses, potential biomarker research, ncRNA axis/network construction, impacts on phenotypes, therapeutic target seeking, maintenance of nucleic acid stability and protein binding research. In addition, we summarize the current situation of and problems associated with circRNAs in immune research, highlight the applications and prospects of circRNAs in the treatment of immune-related diseases, and provide new insight into future directions and new strategies for laboratory research and clinical applications.

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“…Overexpression of circRNA SNRK can significantly reduce myocardial cell apoptosis and promote cardiac repair in myocardial infarction rats ( 14 ). Another study showed that circRNA Ube3a derived from M2 macrophages can promote proliferation, migration and phenotypic transformation of cardiac fibroblasts (CFs) cells by targeting miR-138-5p/RHOC axis, aggravating cardiac fibrosis after AMI ( 15 ). In addition, circ_0023461 silencing protects cardiomyocytes from hypoxia-induced dysfunction by targeting miR-370-3p/PDE4D axis ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of circRNA-miRNA-mRNA Regulatory Network and Novel Potential Biomarkers in Acute Myocardial Infarction

Lei

et al. 2022

Front. Cardiovasc. Med.

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BackgroundCircular RNA (circRNA) plays an important role in the regulation of gene expression and the occurrence of human diseases. However, studies on the role of circRNA in acute myocardial infarction (AMI) are limited. This study was performed to explore novel circRNA-related regulatory networks in AMI, aiming to better understand the molecular mechanism of circRNAs involvement in AMI and provide basis for further scientific research and clinical decision-making.MethodsThe AMI-related microarray datasets GSE160717 (circRNA), GSE31568 (miRNA), GSE61741 (miRNA), and GSE24519 (mRNA) were obtained from the Gene Expression Omnibus (GEO) database. After differential expression analysis, the regulatory relationships between these DERNAs were identified by online databases circBank, circInteractome, miRDB, miRWalk, Targetscan, and then two circRNA-miRNA-mRNA regulatory networks were constructed. Differentially expressed genes (DEGs) in this network were selected followed by enrichment analysis and protein–protein interaction (PPI) analysis. Hub genes were identified using Cytohubba plug-in of Cytoscape software. Hub genes and hub gene-related miRNAs were used for receiver operating characteristic curve (ROC) analysis to identify potential biomarkers. The relative expression levels of these biomarkers were further assessed by GSE31568 (miRNA) and GSE66360 (mRNA). Finally, on the basis of the above analysis, myocardial hypoxia model was constructed to verify the expression of Hub genes and related circRNAs.ResultsA total of 83 DEcircRNAs, 109 CoDEmiRNAs and 1204 DEGs were significantly differentially expressed in these datasets. The up-regulated circRNAs and down-regulated circRNAs were used to construct a circRNA-miRNA-mRNA regulatory network respectively. These circRNA-related DEGs were mainly enriched in the terms of “FOXO signaling pathway,” “T cell receptor signaling pathway,” “MAPK signaling pathway,” “Insulin resistance,” “cAMP signaling pathway,” and “mTOR signaling pathway.” The top 10 hub genes ATP2B2, KCNA1, GRIN2A, SCN2B, GPM6A, CACNA1E, HDAC2, SRSF1, ANK2, and HNRNPA2B1 were identified from the PPI network. Hub genes GPM6A, SRSF1, ANK2 and hub gene-related circRNAs hsa_circ_0023461, hsa_circ_0004561, hsa_circ_0001147, hsa_circ_0004771, hsa_circ_0061276, and hsa_circ_0045519 were identified as potential biomarkers in AMI.ConclusionIn this study, the potential circRNAs associated with AMI were identified and two circRNA-miRNA-mRNA regulatory networks were constructed. This study explored the mechanism of circRNA involvement in AMI and provided new clues for the selection of new diagnostic markers and therapeutic targets for AMI.

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CircUbe3a from M2 macrophage-derived small extracellular vesicles mediates myocardial fibrosis after acute myocardial infarction

Cited by 86 publications

References 49 publications

Emerging roles of circRNAs in the pathological process of myocardial infarction

Emerging roles of circRNAs in the pathological process of myocardial infarction

Past, Present and Future: The Relationship Between Circular RNA and Immunity

Comprehensive Analysis of circRNA-miRNA-mRNA Regulatory Network and Novel Potential Biomarkers in Acute Myocardial Infarction

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