Transcriptome analysis reveals key pathways that vary in patients with paroxysmal and persistent atrial fibrillation.
The present study evaluated mRNA and long non-coding RNA (lncRNA) expression profiles and the pathways involved in paroxysmal atrial fibrillation (ParoAF) and persistent atrial fibrillation (PersAF). Nine left atrial appendage (LAA) tissues collected from the hearts of patients with AF (patients with ParoAF=3; and patients with PersAF=3) and healthy donors (n=3) were analyzed by RNA sequencing. Differentially expressed (DE) mRNAs and lncRNAs were identified by |Log2 fold change|>2 and P<0.05. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway enrichment, protein-protein interaction network and mRNA-lncRNA interaction network analyses of DE mRNA and mRNA at the upstream/downstream of DE lncRNA were conducted. A total of 285 and 275 DE mRNAs, 575 and 583 DE lncRNAs were detected in ParoAF and PersAF samples compared with controls, respectively. PI3K/Akt and transforming growth factor-β signaling pathways were significantly enriched in the ParoAF_Control and the calcium signaling pathway was significantly enriched in the PersAF_Control. Cis and trans analyses revealed some important interactions in DE mRNAs and lncRNA, including an interaction of GPC-AS2 with dopachrome tautomerase, and phosphodiesterase 4D and cAMP-specific with XLOC_110310 and XLOC_137634. Overall, the present study provides a molecular basis for future clinical studies on ParoAF and PersAF.
Sun H
，Shao Y
《-》
Identification of Long Non-Coding RNA and Circular RNA Expression Profiles in Atrial Fibrillation.
Long non-coding RNA (lncRNA) and circular RNA (circRNA) have both been found to play important roles in cardiovascular diseases, including myocardial infarction, heart failure, and atherosclerosis. However, the role of lncRNA and circRNA in atrial fibrillation (AF) has rarely been investigated. This study aimed to identify lncRNA and circRNA expression profiles in AF patients.
Atrial tissues from seven patients with AF and seven matched controls were collected. The lncRNA and circRNA expression profiles of atrial tissues were identified using Hiseq/Proton RNA sequencing. Validation was performed by reverse transcription quantitative real-time PCR (qRT-PCR) on 35 pairs of AF patients and controls. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A competing endogenous RNA (ceRNA) network was constructed.
A total of 557 lncRNAs and 280 circRNAs were significantly differentially expressed with fold change >1.5 (p<0.05). An lncRNA Voltage Dependent Anion Channel 2 Pseudogene 2 (VDAC2P2) and two circRNAs chr13_41887361_41865736_-21625 and chr13_100368574_100301460_-67114 were validated, using qRT-PCR, to have significantly different expression levels. GO and KEGG pathway analysis showed that some pathways such as ribosome and chromatin modification, Rap1 signalling and cardiac muscle contraction were involved in the pathogenesis of AF. Competing endogenous RNAs were predicted based on constructional network analysis. The LncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks were constructed by co-expressing lncRNA/circRNA and mRNAs, which were competitively combined with miRNAs.
This study characterised lncRNA and circRNA expression and their interaction with mRNA and miRNA in AF.
Wu N
，Li J
，Chen X
，Xiang Y
，Wu L
，Li C
，Zhang H
，Tong S
，Zhong L
，Li Y
... -
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Comprehensive analysis of the coding and non-coding RNA transcriptome expression profiles of hippocampus tissue in tx-J animal model of Wilson's disease.
Wilson's disease (WD) is an autosomal recessive disorder with a genetic basis. The predominant non-motor symptom of WD is cognitive dysfunction, although the specific genetic regulatory mechanism remains unclear. Tx-J mice, with an 82% sequence homology of the ATP7B gene to the human gene, are considered the most suitable model for WD. This study employs deep sequencing to investigate the differences in RNA transcript profiles, both coding and non-coding, as well as the functional characteristics of the regulatory network involved in WD cognitive impairment. The cognitive function of tx-J mice was evaluated using the Water Maze Test (WMT). Long non-coding RNA (lncRNA), circular RNA (circRNA), and messenger RNA (mRNA) profiles were analyzed in the hippocampal tissue of tx-J mice to identify differentially expressed RNAs (DE-RNAs). Subsequently, the DE-RNAs were used to construct protein-protein interaction (PPI) networks, as well as DE-circRNAs and lncRNAs-associated competing endogenous RNA (ceRNA) expression networks, and coding-noncoding co-expression (CNC) networks. To elucidate their biological functions and pathways, the PPI and ceRNA networks were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A total of 361 differentially expressed mRNAs (DE-mRNAs), comprising 193 up-regulated and 168 down-regulated mRNAs, 2627 differentially expressed long non-coding RNAs (DE-lncRNAs), consisting of 1270 up-regulated and 1357 down-regulated lncRNAs, and 99 differentially expressed circular RNAs (DE-circRNAs), consisting of 68 up-regulated and 31 down-regulated circRNAs, were observed in the tx-J mice group when compared to the control mice group. Gene Ontology (GO) and pathway analyses revealed that DE-mRNAs were enriched in cellular processes, calcium signaling pathways, and mRNA surveillance pathways. In contrast, the DE-circRNAs-associated competing endogenous RNA (ceRNA) network was enriched for covalent chromatin modification, histone modification, and axon guidance, whereas the DE-lncRNAs-associated ceRNA network was enriched for dendritic spine, regulation of cell morphogenesis involved in differentiation, and mRNA surveillance pathway. The study presented the expression profiles of lncRNA, circRNA, and mRNA in the hippocampal tissue of tx-J mice. Furthermore, the study constructed PPI, ceRNA, and CNC expression networks. The findings are significant in comprehending the function of regulatory genes in WD associated with cognitive impairment. These results also offer valuable information for the diagnosis and treatment of WD.
Wang D
，Xie D
，Zhang J
，Cai B
，Yang B
，Zhou L
，Huang X
... -
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