Construction of atrial fibrillation-related circRNA/lncRNA-miRNA-mRNA regulatory network and analysis of potential biomarkers.

The specific pathogenesis of atrial fibrillation (AF) remains unclear. In this study, we examined the expression of differential messenger RNAs (mRNAs), circular RNAs (circRNAs), and long-stranded noncoding RNAs (lncRNAs) from human peripheral blood mononuclear cells to initially construct a circRNA/lncRNA-miRNA-mRNA ceRNA regulatory network to explore the pathogenesis of AF and to screen for potential biomarkers. A total of four pairs of AF cases and healthy subjects were selected to detect differentially expressed mRNAs, circRNAs, and lncRNAs in peripheral blood mononuclear cells by microarray analysis. And 20 pairs of peripheral blood from AF patients and healthy subjects were selected for validation of mRNA, circRNA, and lncRNA by quantitative real-time PCR (qRT-PCR).The relevant ceRNA networks were constructed by GO and KEGG and correlation analysis. The results showed that compared with healthy subjects, there were 813 differentially expressed mRNAs (DEmRNAs) in peripheral blood monocytes of AF, including 445 upregulated genes and 368 downregulated genes, 120 differentially expressed circRNAs (DEcircRNAs), including 65 upregulated and 55 downregulated, 912 differentially expressed lncRNAs (DElncRNAs), including 531 upregulated and 381 downregulated lncRNAs. GO and KEGG analysis of DERNA revealed the biological processes and pathways involved in AF. Based on microarray data and predicted miRNAs, a ceRNA network containing 34 mRNAs, 212 circRNAs, 108 lncRNAs, and 38 miRNAs was constructed. We revealed a novel ceRNA network in AF and showed that downregulated XIST, circRNA_2773, and CADM1 were negatively correlated with miR-486-5p expression and had a potential targeting relationship with miR-486-5p.

Wen JL ，Ruan ZB ，Wang F ，Chen GC ，Zhu JG ，Ren Y ，Zhu L ... -  《-》

Identification of Serum Exosome-Derived circRNA-miRNA-TF-mRNA Regulatory Network in Postmenopausal Osteoporosis Using Bioinformatics Analysis and Validation in Peripheral Blood-Derived Mononuclear Cells.

Osteoporosis is one of the most common systemic metabolic bone diseases, especially in postmenopausal women. Circular RNA (circRNA) has been implicated in various human diseases. However, the potential role of circRNAs in postmenopausal osteoporosis (PMOP) remains largely unknown. The study aims to identify potential biomarkers and further understand the mechanism of PMOP by constructing a circRNA-associated ceRNA network. The PMOP-related datasets GSE161361, GSE64433, and GSE56116 were downloaded from the Gene Expression Omnibus (GEO) database and were used to obtain differentially expressed genes (DEGs). Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to determine possible relevant functions of differentially expressed messenger RNAs (mRNAs). The TRRUST database was used to predict differential transcription factor (TF)-mRNA regulatory pairs. Afterwards, combined CircBank and miRTarBase, circRNA-miRNA as well as miRNA-TF pairs were constructed. Then, a circRNA-miRNA-TF-mRNA network was established. Next, the correlation of mRNAs, TFs, and PMOP was verified by the Comparative Toxicogenomics Database. And expression levels of key genes, including circRNAs, miRNAs, TFs, and mRNAs in the ceRNA network were further validated by quantitative real-time PCR (qRT-PCR). Furthermore, to screen out signaling pathways related to key mRNAs of the ceRNA network, Gene Set Enrichment Analysis (GSEA) was performed. A total of 1201 DE mRNAs, 44 DE miRNAs, and 1613 DE circRNAs associated with PMOP were obtained. GO function annotation showed DE mRNAs were mainly related to inflammatory responses. KEGG analysis revealed DE mRNAs were mainly enriched in osteoclast differentiation, rheumatoid arthritis, hematopoietic cell lineage, and cytokine-cytokine receptor interaction pathways. We first identified 26 TFs and their target mRNAs. Combining DE miRNAs, miRNA-TF/mRNA pairs were obtained. Combining DE circRNAs, we constructed the ceRNA network contained 6 circRNAs, 4 miRNAs, 4 TFs, and 12 mRNAs. The expression levels of most genes detected by qRT-PCR were generally consistent with the microarray results. Combined with the qRT-PCR validation results, we eventually identified the ceRNA network that contained 4 circRNAs, 3 miRNAs, 3 TFs, and 9 mRNAs. The GSEA revealed that 9 mRNAs participate in many important signaling pathways, such as "olfactory transduction", "T cell receptor signaling pathway", and "neuroactive ligand-receptor interaction". These pathways have been reported to the occurrence and development of PMOP. To sum up, key mRNAs in the ceRNA network may participate in the development of osteoporosis by regulating related signal pathways. A circRNA-associated ceRNA network containing TFs was established for PMOP. The study may help further explore the molecular mechanisms and may serve as potential biomarkers or therapeutic targets for PMOP.

Dong Q ，Han Z ，Tian L 《Frontiers in Endocrinology》

Identification of a Plasma Exosomal lncRNA- and circRNA-Based ceRNA Regulatory Network in Patients With Lung Adenocarcinoma.

Exosomes have been established to be enriched with various long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) that exert various biological effects. However, the lncRNA- and circRNA-mediated coexpression competing endogenous RNA (ceRNA) regulatory network in exosomes derived from the plasma of patients with lung adenocarcinoma (LUAD) remains elusive. This study enrolled nine patients with lung adenocarcinoma and three healthy individuals, and the differential expression of messenger RNAs (mRNAs), lncRNAs, and circRNAs was detected using microarray analysis, while microRNAs (miRNAs) were detected through RNA sequencing. Additionally, bioinformatics algorithms were applied to evaluate the lncRNA-miRNA-mRNAs/circRNA-miRNA-mRNA network. Differentially expressed cicRNAs were identified via quantitative reverse transcription polymerase chain reaction (RT-qPCR). A total of 1016 lncRNAs, 1396 circRNAs, 45 miRNAs, and 699 mRNAs were differentially expressed in the plasma exosomes of patients with LUAD compared with healthy controls. Among them, 881 lncRNAs were upregulated and 135 were downregulated, 916 circRNAs were upregulated while 480 were downregulated, 45 miRNAs were upregulated while none were downregulated, and 591 mRNAs were upregulated while 108 were downregulated (p ≤ 0.05, and fold change ≥ 2). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the biological functions of differentially expressed RNAs. Meanwhile, the RNA networks displayed the regulatory relationship between dysregulated RNAs. Finally, RT-qPCR validated that the expression of circ-0033861, circ-0043273, and circ-0011959 was upregulated in the plasma exosome of patients with LUAD compared to healthy controls (p = 0.0327, p = 0.0002, p = 0.0437, respectively). This study proposed a newly discovered ncRNA-miRNA-mRNA/circRNA-miRNA-mRNA ceRNA network and identified that the expression of circulating circ-0033861, circ-0043273, and circ-0011959 was up-regulated in the plasma exosomes of patients with LUAD, offering valuable insights for exploring the potential function of exosomal noncoding RNA and identifying potential biomarkers for LUAD.

Zhu W ，Zhang H ，Tang L ，Fang K ，Lin N ，Huang Y ，Zhang Y ，Le H ... -  《-》

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 ... -  《-》

Identification of atrial fibrillation-related circular RNAs and constructing the integrative regulatory network of circular RNAs, microRNAs and mRNAs by bioinformatics analysis.

Zhai Z ，Qin T ，Liu F ，Han L ，Zhou H ，Li Q ，Xia Z ，Li J ... -  《-》