Integrated analysis of competing endogenous RNA networks in peripheral blood mononuclear cells of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complicated pathogenesis, and its aetiology has not been clearly unveiled. The lack of effective diagnosis and treatment methods makes it necessary to explore the molecular mechanism of SLE. We aimed to identify some critical signalling pathways and key competing endogenous RNAs (ceRNAs) underlying the molecular mechanism of SLE and to map out the systematic signalling networks by integrating the data on different kinds of RNAs. Peripheral blood mononuclear cells (PBMCs) were collected from both SLE patients and healthy subjects, RNA was extracted from the PBMCs, and RNA libraries including ribosomal RNA-depleted strand-specific libraries and small RNA libraries were built for deep RNA sequencing (RNA-seq). RNA-seq yielded differential expression profiles of lncRNAs/circRNAs/miRNAs/mRNAs related to SLE. The DAVID database (v. 6.8) was employed for Gene Ontology (GO) and KEGG pathway analysis. ceRNA networks (circRNA/lncRNA-miRNA-mRNA) were constructed and visualized using Cytoscape software (v. 3.5.0). The TargetScan and miRanda databases were used to predict target relationships in ceRNA networks. qRT-PCR was used to verify our data. Differential expression of ceRNAs related to SLE was detected in SLE patients' PBMCs: 644 mRNAs (384 upregulated, 260 downregulated), 326 miRNAs (223 upregulated, 103 downregulated), 221 lncRNAs (79 upregulated, 142 downregulated), and 31 circRNAs (21 upregulated, 10 downregulated). We drew ceRNA signalling networks made up of the differentially expressed mRNAs/miRNAs/lncRNAs/circRNAs mentioned above, and the hub genes included IRF5, IFNAR2, TLR7, IRAK4, STAT1, STAT2, C2, and Tyk2. These hub genes were involved in ceRNA signalling pathways, such as the IL-17 signalling pathway and type I interferon signalling pathway. We explored the differential expression profiles of various kinds of ceRNAs and integrated signalling networks constructed by ceRNAs. Our findings offer new insights into the pathogenesis of SLE and hint at therapeutic strategies.

Song W ，Qiu J ，Yin L ，Hong X ，Dai W ，Tang D ，Liu D ，Dai Y ... -  《Journal of Translational Medicine》

Full high-throughput sequencing analysis of differences in expression profiles of long noncoding RNAs and their mechanisms of action in systemic lupus erythematosus.

Ye H ，Wang X ，Wang L ，Chu X ，Hu X ，Sun L ，Jiang M ，Wang H ，Wang Z ，Zhao H ，Yang X ，Wang J ... -  《-》

The circRNA-miRNA-mRNA regulatory network in plasma and peripheral blood mononuclear cells and the potential associations with the pathogenesis of systemic lupus erythematosus.

This study aimed to explore the possible role of plasma and peripheral blood mononuclear cells (PBMCs) circular RNA (circRNA) in systemic lupus erythematosus (SLE). Total RNA was extracted from blood plasma samples obtained from 10 patients with SLE and 10 healthy controls and subjected to microarray analysis to define the profile of circRNA expression. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) amplification was conducted. The overlapped circRNA between PBMCs and plasma was performed, the interactions with microRNAs were predicted, the miRNA target mRNA was predicted, and the GEO database was used. The Gene ontology and pathway analysis was performed. One hundred thirty-one upregulated and 314 significantly downregulated circRNAs were identified in the plasma of patients with SLE by the Fold change criteria (≥ 2.0) and P < 0.05. The qRT-PCR results showed that the expression of has-circRNA-102531, has-circRNA-103984, and has-circRNA-104262 was increased in plasma of SLE, and the expression of has-circRNA-102972, has-circRNA-102006, has-circRNA-104313 was decreased in plasma of SLE. Twenty-eight upregulated circRNAs and 119 downregulated circRNAs were overlapped from PBMCs and plasma, and ubiquitination was enriched. Furthermore, the circRNA-miRNA-mRNA network was constructed in SLE after analyzing dataset GSE61635 from GEO. The circRNA-miRNA-mRNA network comprises 54 circRNAs, 41 miRNAs, and 580 mRNAs. In addition, the TNF signaling pathway and the MAPK pathway were enriched from the mRNA of the miRNA target. We first revealed the differentially expressed circRNAs in plasma and PBMCs, and then the circRNA-miRNA-mRNA network was constructed. The network's circRNAs could be a potential diagnostic biomarker and potentially play an important role in the pathogenesis and development of SLE. Key Points • This study analyzed the circRNAs expression profiles combined with the plasma and PBMCs, which provided a comprehensive overview of circRNAs expression patterns in SLE. • The network of the circRNA-miRNA-mRNA in SLE was constructed, which contributes to a better understanding of the pathogenesis and development of SLE.

Zheng F ，Tan L ，Zhang F ，Li S ，Lai Z ，Xu H ，Xiong Z ，Dai Y ... -  《-》

Reconstruction and analysis of the aberrant lncRNA-miRNA-mRNA network in systemic lupus erythematosus.

Xu H ，Chen W ，Zheng F ，Tang D ，Liu D ，Wang G ，Xu Y ，Yin L ，Zhang X ，Dai Y ... -  《-》

Construction and functional enrichment analysis of the competitive endogenous RNA regulatory network for nonarteritic anterior ischemic optic neuropathy based on high-throughput sequencing.

Based on the transcriptome high-throughput sequencing of nonarteritic anterior ischemic optic neuropathy (NAION), this study constructed a competitive endogenous RNA (ceRNA) network, enriched and analyzed it, screened long noncoding (lnc)RNAs and circular (circ)RNAs that may participate in the competitive endogenous mechanism in NAION, and inferred its function. Four milliliters of peripheral blood from NAION patients and the control group was extracted from clinical samples, transcriptome high-throughput sequencing was performed, and the sequencing data were visualized. Based on the principle of the ceRNA network, the lncRNA-micro (mi)RNA-messenger (m)RNA interaction axis and circRNA-miRNA‒mRNA interaction axes were constructed. The differentially expressed genes (DEGs) in the interaction axis were enriched and analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the functions and signalling pathways of lncRNAs and circRNAs in the interaction network were speculated. Fifty-one circRNAs were differentially expressed in the sequencing data: 25 were upregulated, and 26 were downregulated. For 996 differentially expressed lncRNAs, 317 were upregulated and 679 were downregulated, and for 1161 differentially expressed mRNAs, 698 were upregulated and 463 were downregulated. Thirty-three differentially expressed miRNAs, upregulated miRNA 18 and downregulated miRNA 15 were identified. After screening, 13 coexpressed mRNAs, 15 lncRNAs, and 3 miRNAs were finally constructed in the lncRNA-miRNA-mRNA network, and the circRNA-miRNA-mRNA network was constructed by 159 mRNAs, 26 miRNAs, and 34 circRNAs. In the lncRNA network, GO enrichment analysis obtained 182 biological processes, 12 cell components and 38 molecular functions, which are related mainly to the regulation of the activity of proteins and enzymes such as cyclic nucleotide-dependent protein kinase activity and magnesium ion-dependent protein serine/threonine phosphatase activity. KEGG analysis involved mainly the forkhead box O (FoxO) signalling pathway, apelin signalling pathway, etc. In the circRNA enrichment results, 353 biological processes, 52 cell components, and 45 molecular functions were obtained, involving mainly calcium channel regulation, neutrophil activation, mRNA transport, and metabolism. KEGG mainly involved the Wnt signalling pathway, apelin signalling pathway, Hippo signalling pathway, oxytocin signalling pathway, etc. This paper provides a new idea for lncRNAs and circRNAs to mediate the occurrence and development of NAION through the ceRNA mechanism. This study lays a foundation for the in-depth study of the pathogenesis of NAION.

Zhang M ，Wang X 《-》