DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43

Hou, Jian; Yuan, Yue; Hu, Bing; Xu, Guangtao; Su, Ruibing; Lv, Linhua; Huang, Jiaxing; Yao, Jianping; Guan, Yuanjun; Wang, Keke; Wu, Zhongkai

doi:10.21470/1678-9741-2019-0033

Cited by 14 publications

(16 citation statements)

References 26 publications

(29 reference statements)

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“…Our KEGG enrichment analysis revealed that these DEGs were associated with regulation of actin cytoskeleton, phagosome, and leukocyte transendothelial migration. As previous studies, it has been found that several genes could regulate the cytoskeleton arrangement of cardiomyocytes in AF [22]. Atrial autophagic flux could be activated in response to AF [23].…”

Section: Discussionsupporting

confidence: 61%

Multiomics Analysis of Genetics and Epigenetics Reveals Pathogenesis and Therapeutic Targets for Atrial Fibrillation

Liu

Huang

Wei

et al. 2021

BioMed Research International

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Objective. This study is aimed at understanding the molecular mechanisms and exploring potential therapeutic targets for atrial fibrillation (AF) by multiomics analysis. Methods. Transcriptomics and methylation data of AF patients were retrieved from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) and differentially methylated sites between AF and normal samples were screened. Then, highly expressed and hypomethylated and lowly expressed and hypermethylated genes were identified for AF. Weighted gene coexpression network analysis (WGCNA) was presented to construct AF-related coexpression networks. 52 AF blood samples were used for whole exome sequence. The mutation was visualized by the maftools package in R. Key genes were validated in AF using independent datasets. Results. DEGs were identified between AF and controls, which were enriched in neutrophil activation and regulation of actin cytoskeleton. RHOA, CCR2, CASP8, and SYNPO2L exhibited abnormal expression and methylation, which have been confirmed to be related to AF. PCDHA family genes had high methylation and low expression in AF. We constructed two AF-related coexpression modules. Single-nucleotide polymorphism (SNP) was the most common mutation type in AF, especially T > C . MUC4 was the most frequent mutation gene, followed by PHLDA1, AHNAK2, and MAML3. There was no statistical difference in expression of AHNAK2 and MAML3, for AF. PHLDA1 and MUC4 were confirmed to be abnormally expressed in AF. Conclusion. Our findings identified DEGs related to DNA methylation and mutation for AF, which may offer possible therapeutic targets and a new insight into the pathogenesis of AF from a multiomics perspective.

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Section: Discussionsupporting

confidence: 61%

Multiomics Analysis of Genetics and Epigenetics Reveals Pathogenesis and Therapeutic Targets for Atrial Fibrillation

Liu

Huang

Wei

et al. 2021

BioMed Research International

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“…Previous studies had shown that the expression of CLIC1 [211], ARPC1B [212], FLNA (filamin A) [213], HILPDA (hypoxia inducible lipid droplet associated) [214], RTN3 [215], G0S2 [216], CALU (calumenin) [ [239], NCOA2 [240], ZBTB16 [241], TFAM (transcription factor A, mitochondrial) [242], RASAL2 [243], NDUFB6 [244], HELZ2 [245] and CIITA (class II major histocompatibility complex transactivator) [246] were reported to be expressed in obesity, but these genes might be novel target for HF. TGFB1 [247], CD63 [248], DACT1 [249] and PSMB10 [250] have been reported to be crucial for the progression of atrial fibrillation. FAM20C [251] and CD74 [252] are important in the development of cardiac arrhythmia.…”

Section: Discussionmentioning

confidence: 99%

“…HSPA5 [225], NMB (neuromedin B) [226], ELP5 [227], NLGN2 [228], RAB23 [229], MBOAT7 [230], CEP19 [231], PFKP (phosphofructokinase, platelet) [232], TKT (transketolase) [233], P4HB [234], CRYM (crystallin mu) [235], AMT (aminomethyltransferase) [236], MACROD2 [237], NUDT3 [238], DLD (dihydrolipoamide dehydrogenase) [239], NCOA2 [240], ZBTB16 [241], TFAM (transcription factor A, mitochondrial) [242], RASAL2 [243], NDUFB6 [244], HELZ2 [245] and CIITA (class II major histocompatibility complex transactivator) [246] were reported to be expressed in obesity, but these genes might be novel target for HF. TGFB1 [247], CD63 [248], DACT1 [249] and PSMB10 [250] have been reported to be crucial for the progression of atrial fibrillation. FAM20C [251] and CD74 [252] are important in the development of cardiac arrhythmia.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers, pathways and potential therapeutic targets for heart failure using bioinformatics analysis

Vastrad¹,

Vastrad²

2021

Preprint

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Heart failure (HF) is a complex cardiovascular diseases associated with high mortality. To discover key molecular changes in HF, we analyzed next-generation sequencing (NGS) data of HF. In this investigation, differentially expressed genes (DEGs) were analyzed using limma in R package from GSE161472 of the Gene Expression Omnibus (GEO). Then, gene enrichment analysis, protein-protein interaction (PPI) network, miRNA-hub gene regulatory network and TF-hub gene regulatory network construction, and topological analysis were performed on the DEGs by the Gene Ontology (GO), REACTOME pathway, STRING, HiPPIE, miRNet, NetworkAnalyst and Cytoscape. Finally, we performed receiver operating characteristic curve (ROC) analysis of hub genes. A total of 930 DEGs 9464 up regulated genes and 466 down regulated genes) were identified in HF. GO and REACTOME pathway enrichment results showed that DEGs mainly enriched in localization, small molecule metabolic process, SARS-CoV infections and the citric acid (TCA) cycle and respiratory electron transport. Subsequently, the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed, and 10 hub genes in these network were focused on by centrality analysis and module analysis. Furthermore, data showed that HSP90AA1, ARRB2, MYH9, HSP90AB1, FLNA, EGFR, PIK3R1, CUL4A, YEATS4 and KAT2B were good diagnostic values. In summary, this study suggests that HSP90AA1, ARRB2, MYH9, HSP90AB1, FLNA, EGFR, PIK3R1, CUL4A, YEATS4 and KAT2B may act as the key genes in HF.

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“…The RA appendages of normal hearts were obtained from autopsies (two cases) and provided by the Department of Forensic Pathology of Shantou University Medical College and the Department of Forensic Pathology of Jiaxing University Medical College, which were reported previously [ 12 ] . Both patients were male, and they were 19 and 23 years old.…”

Section: Methodsmentioning

confidence: 99%

Does Decreased SNX10 Serve as a Novel Risk Factor in Atrial Fibrillation of the Valvular Heart Disease? – A Case-Control Study

Yao¹,

Hou²,

Lv³

et al. 2021

Braz J Cardiovasc Surg

Self Cite

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Introduction Atrial fibrillation (AF) is the most common sustained arrhythmia. Sorting nexin 10 (SNX10) has been reported to be an important regulator in embryonic development and human diseases, however, little is known about its role in cardiac disease. The aim of this study was to investigate the clinical significance of SNX10 expression in AF. Methods Nineteen valvular heart disease patients with AF and nine valvular heart disease patients with sinus rhythm (SR) were enrolled. Atrial tissue samples from patients undergoing open heart surgery were examined. Atrial tissues of normal hearts were obtained from two cases’ autopsies. The SNX10 expression and its associations with the degree of fibrosis were analyzed by immunohistochemistry and Masson’s trichrome staining. Results SNX10 expression was detected in the cytoplasm of cardiac cells in human myocardial tissue. The SNX10 expression level was higher in the SR group than in the AF group ( P =0.023). SNX10 expression was negatively associated with the degree of fibrosis ( P =0.017, Spearman rho=-0.447), the New York Heart Association degree ( P =0.003, Spearman rho=-0.545), left atrial diameter ( P =0.038, Spearman rho=-0.393), right atrial diameter ( P =0.043, Spearman rho=-0.386), and the brain natriuretic peptide (BNP) level 24 hours after surgery ( P =0.030, Spearman rho=-0.426), but not the BNP level before surgery and 72 hours after surgery. No statistical significance was observed between SNX10 and the level of troponin T and C-reactive protein. Conclusion Decreased SNX10 might serve as a potential risk factor in AF of the valvular heart disease.

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DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43

Cited by 14 publications

References 26 publications

Multiomics Analysis of Genetics and Epigenetics Reveals Pathogenesis and Therapeutic Targets for Atrial Fibrillation

Multiomics Analysis of Genetics and Epigenetics Reveals Pathogenesis and Therapeutic Targets for Atrial Fibrillation

Identification of biomarkers, pathways and potential therapeutic targets for heart failure using bioinformatics analysis

Does Decreased SNX10 Serve as a Novel Risk Factor in Atrial Fibrillation of the Valvular Heart Disease? – A Case-Control Study

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