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

• Published in: Journal of translational medicine Vol. 19; no. 1; pp. 1 - 15
• Main Authors: Song, Wencong, Qiu, Jie, Yin, Lianghong, Hong, Xiaoping, Dai, Weier, Tang, Donge, Liu, Dongzhou, Dai, Yong
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 21.08.2021; BioMed Central; BMC
• Subjects: Autoimmune diseases; ceRNAs; Development and progression; Disease; Genetic aspects; Genomes; Health aspects; Integrative analysis; Interferon; Interleukin 17; Kinases; Leukocytes (mononuclear); Lupus; Lymphocytes; Medical diagnosis; MicroRNAs; miRNA; Monocytes; mRNA; Pathogenesis; Patients; Peripheral blood mononuclear cells; Physiological aspects; RNA; RNA sequencing; rRNA; Signal transduction; SLE; Stat1 protein; Stat2 protein; Systemic lupus erythematosus; TLR7 protein; Toll-like receptors; Tyk2 protein; China; United States > US
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-021-03033-8

Background 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. Methods 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. Results 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. Conclusions 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. Keywords: ceRNAs, Integrative analysis, SLE, RNA sequencing