Dataset Information

Genome-wide analysis of circular RNA expression profiles in patients with atrial fibrillation.

ABSTRACT: Atrial fibrillation (AF) is one of the most common clinical cardiac arrhythmias. This study was done to screen differentially expressed circular RNAs (circRNAs) in human monocytes from patients with AF and healthy controls using microarray, and preliminarily explore the role of circRNAs in the development of AF. The expression of circRNAs in peripheral blood monocytes of 4 AF patients and 4 healthy donors was detected by chip technology and validated by qRT-PCR. Differentially expressed genes were screened out. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify the function of differentially expressed genes and related pathways. Potential connections between circRNAs and miRNAs were explored by using Cytoscape. 120 differentially expressed circRNAs (FC?2, P<0.05) were preliminarily screened by circRNA microarray, of which 65 were up-regulated and 55 down-regulated. All of 4 upregulated circRNAs (circRNA_0031, circRNA_1837, circRNA_5901 and circRNA_7571) and 3 out of 4 downregulated circRNAs (circRNA_5801, circRNA_7386 and circRNA_7577) were randomly confirmed by RT-PCR. GO and KEGG analysis suggested that differentially expressed circRNA-related genes are mainly involved in inflammation, immunity, and signaling transduction. CircRNA_7571, circRNA_4648, circRNA_4631 and circRNA_2875 were the first 4 circRNAs with the most binding nodes in the co-expression network. In addition, hsa-miR-328 was the highest positively correlated miRNA in the networks. Our findings demonstrated that there were differentially expressed circRNAs in human monocytes from AF patients. circRNA_7571, circRNA_4648, circRNA_4631 and circRNA_2875 were the first 4 circRNAs with the most binding nodes in the co-expression network. hsa-miR-328 was the largest node that interacted with circRNAs in the co-expression network. circRNAs-hsa-miR-328 network may play a critical role in the pathophysiology and mechanism of AF.

SUBMITTER: Ruan ZB

PROVIDER: S-EPMC7476958 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Genome-wide analysis of circular RNA expression profiles in patients with atrial fibrillation.

Ruan Zhong-Bao ZB Wang Fei F Bao Ting-Ting TT Yu Qiu-Ping QP Chen Ge-Cai GC Zhu Li L

International journal of clinical and experimental pathology 20200801 8

Atrial fibrillation (AF) is one of the most common clinical cardiac arrhythmias. This study was done to screen differentially expressed circular RNAs (circRNAs) in human monocytes from patients with AF and healthy controls using microarray, and preliminarily explore the role of circRNAs in the development of AF. The expression of circRNAs in peripheral blood monocytes of 4 AF patients and 4 healthy donors was detected by chip technology and validated by qRT-PCR. Differentially expressed genes we ...[more]

PMID: 32922589

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Project description:BackgroundCircular RNA (circRNA) is a noncoding RNA that forms a closed-loop structure, and its abnormal expression may cause disease. We aimed to find potential network for circRNA-related competitive endogenous RNA (ceRNA) in atrial fibrillation (AF).MethodsThe circRNA, miRNA, and mRNA expression profiles in the heart tissue from AF patients were retrieved from the Gene Expression Omnibus database and analyzed comprehensively. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified, followed by the establishment of DEcircRNA-DEmiRNA-DEmRNA regulatory network. Functional annotation analysis of host gene of DEcircRNAs and DEmRNAs in ceRNA regulatory network was performed. In vitro experiment and electronic validation were used to validate the expression of DEcircRNAs, DEmiRNAs, and DEmRNAs.ResultsA total of 1611 DEcircRNAs, 51 DEmiRNAs, and 1250 DEmRNAs were identified in AF. The DEcircRNA-DEmiRNA-DEmRNA network contained 62 circRNAs, 14 miRNAs, and 728 mRNAs. Among which, two ceRNA regulatory pairs of hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 were identified. In addition, six miRNA-mRNA regulatory pairs including hsa-miR-34c-5p-INMT, hsa-miR-1253-DDIT4L, hsa-miR-508-5p-SMOC2, hsa-miR-943-ACTA1, hsa-miR-338-3p-WIPI1, and hsa-miR-199a-3p-RAP1GAP2 were also obtained. MTOR was a significantly enriched signaling pathway of host gene of DEcircRNAs. In addition, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy were remarkably enriched signaling pathways of DEmRNAs in DEcircRNA-DEmiRNA-DEmRNA regulatory network. The expression validation of hsa-circRNA-402565, hsa-miR-34c-5p, hsa-miR-188-5p, SPON1, DDIT4L, SMOC2, and WIPI1 was consistent with the integrated analysis.ConclusionWe speculated that hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 interaction pairs may be involved in AF.

Project description:Introduction: Gefitinib is a selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) widely used in lung adenocarcinoma (LUAD) patients harboring sensitive EGFR mutations. Although it has a good initial efficacy, acquired resistance to gefitinib is eventually inevitable. Studies have shown that circular RNA (circRNA) is involved in the development of acquired resistance to different anti-cancer drugs, but the comprehensive analysis of its expression profile and functions on acquired gefitinib resistance remains poor. Methods: To explore the aberrant circRNAs expression profiles, we collected peripheral plasma samples from 4 gefitinib-sensitive and 4 gefitinib-resistant patients for performing microarray analysis. Candidates of differentially expressed circRNAs were used and analyzed by bioinformatics modalities including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and a constructed circRNA-microRNA RNA network. The differential expression of selected circRNAs was verified by quantitative real-time PCR (qRT-PCR). Results: A total of 2571 circRNAs with significantly different expression between the groups were identified by microarray analysis. GO, KEGG, and pathway enrichment analyses reveal that these differentially expressed circRNAs (DECs) were complicated in many biological pathways that may be related to EGFR-TKI resistance such as ABC transporter and PI3K-Akt pathways. A circRNA-microRNA network was constructed by 10 circRNAs potentially involved in EGFR-TKI resistance togethering with their corresponding microRNAs (miRNAs). Consistent with the results of microarray assay, hsa_circ_0030591 and hsa_circ_0040348 were validated to be upregulated in gefitinib-resistant patients by qRT-PCR. Conclusions: Our study provides valuable data on circRNAs expression profiles detected in liquid biopsy for LUAD patients with acquired gefitinib resistance, and we validate that upregulations of hsa_circ_0030591 and hsa_circ_0040348 may play key roles in EGFR-TKI resistance and thus serving as candidates for biomarker.

Project description:PurposeTo investigate the expression profiles of long noncoding RNAs (lncRNAs) in patients with atrial fibrillation (AF).MethodsThe peripheral blood monocytes of a total of 20 patients with AF and 20 healthy subjects were collected for gene chip technology to detect differentially expressed lncRNAs from 2017.01 to 2017.08. Reverse transcription polymerase chain reaction (RT-PCR) was applied for further verification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify the functions of differentially expressed genes and related pathways.ResultsThere were 19 lncRNAs differentially expressed (FC ≥ 2, P < 0.05), of which 6 were upregulated and 13 were downregulated. Two of three upregulated lncRNAs (P = 0.014 and 0.006 for HNRNPU-AS1 and LINC00861, respectively) and two of three downregulated lncRNAs (P = 0.028 and 0.032 for RP11-443B7.3 and CTD-2616J11.14, respectively) were randomly confirmed by RT-PCR and showed a significantly different expression with the RNA-seq results. GO analysis showed that differentially expressed genes enriched in differentially expressed transcripts in biological process were mainly involved in metabolic process, catabolic process, and biosynthetic process. Differentially expressed transcripts in cellular component were mainly involved in nuclear lumen, organelle lumen, and cytoplasm. Differentially expressed transcripts in molecular function were mainly involved in protein binding, RNA binding, and molecular function. KEGG enrichment pathway analysis showed that some of the enrichment pathways associated with differentially expressed lncRNAs include calcium signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, and Toll-like receptor signaling pathway. HNRNPU-AS1 was the highest positive correlated lncRNA in the networks.ConclusionsThe expression of lncRNA in peripheral blood of AF patients is different from that of normal people. The physiological functions of these differentially expressed lncRNAs may be related to the pathogenesis of AF, which provide experimental basis and new therapeutic target for prognosis and treatment of patients with AF. HNRNPU-AS1 may play an important role in the pathophysiology and mechanisms of AF.

Project description:ObjectiveThis study aimed to investigate the functions of mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) in paroxysmal and persistent atrial fibrillation (AF) patients.MethodsA total of 9 left atrial appendage (LAA) tissues were collected from patients with AF (ParoAF patients = 3 and PersAF patients = 3) and donors (n=3). Genes and circRNAs were identified by per kilobase per million reads (RPKM) and number of circular reads/number of mapped reads/read length (SRPBM), respectively. Differentially expressed mRNAs (DE mRNAs), lncRNAs (DE lncRNAs), and circRNAs (DE circRNAs) were identified by | log2 (Fold Change) | ≥ 2 and p-value < 0.05. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Protein-protein, mRNA-lncRNA, and circRNA-miRNA interaction networks were constructed. In addition, logistic analysis was conducted among AF and circRNAs.ResultsA total of 285 (116 up-regulated and 169 down-regulated) and 275 (110 up-regulated and 165 down-regulated) DE mRNAs, 575 (276 up-regulated and 299 down-regulated) and 583 (330 up-regulated and 253 down-regulated) DE lncRNAs, and 83 (48 up-regulated and 35 down-regulated) and 99 (58 up-regulated and 41 down-regulated) circRNAs were detected in ParoAF and PersAF, respectively, as compared with control. MAPK signal pathway as well as voltage-dependent, L type, and alpha 1C subunit calcium channel (CACNA1C) might participate in AF occurrence by preventing atrial parasympathetic remodeling. Collagen type I alpha 1 (COL1A1) and COL1A2 mostly participated in the enriched GO and KEGG terms and connected with most of the DE mRNAs. The expression of chr10: 69902697|69948883 was a protective factor against PersAF after adjusting for age (p=0.022, 95% CI: 0.003-0.634).ConclusionWe found that some mRNAs, lncRNAs, circRNAs, and pathways play essential roles in AF pathogenesis and development. Moreover, one protective factor against PersAF was detected.

Dataset Information

Genome-wide analysis of circular RNA expression profiles in patients with atrial fibrillation.

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Genome-wide analysis of circular RNA expression profiles in patients with atrial fibrillation.

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