CircRNA expression profiles and function prediction in peripheral blood mononuclear cells of patients with acute ischemic stroke

• Published in: Journal of cellular physiology Vol. 235; no. 3; pp. 2609 - 2618
• Main Authors: Dong, Zhaofei, Deng, Lingna, Peng, Qingxia, Pan, Jingrui, Wang, Yidong
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2020
• Subjects: acute ischemic stroke; Animal tissues; Binding sites; Bioinformatics; Biomarkers; Biomarkers - analysis; Blood; Case-Control Studies; circular RNAs; Computational Biology; Diagnostic systems; Encyclopedias; expression profile; Female; Gene Expression Profiling; Genomes; High-Throughput Nucleotide Sequencing; high‐throughput sequencing; Humans; Ischemia; Ischemic Stroke - mortality; Ischemic Stroke - pathology; Leukocytes (mononuclear); Leukocytes, Mononuclear - cytology; Male; Middle Aged; miRNA; peripheral blood mononuclear cell; Peripheral blood mononuclear cells; Polymerase chain reaction; Prospective Studies; Real-Time Polymerase Chain Reaction; RNA, Circular - analysis; RNA, Circular - biosynthesis; RNA, Circular - genetics; Splicing; Stroke; Therapeutic applications; circular RNAs; acute ischemic stroke; expression profile; high-throughput sequencing; peripheral blood mononuclear cell
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.29165

Most circular RNAs (circRNAs) belong to a novel class of noncoding RNAs that are produced by back‐splicing reactions, and they regulate physiological and pathophysiological processes in human disease. Although circRNA expression has been shown to be altered in the ischemic cerebral tissue in animal studies, the expression profile of circRNA in the patients with acute ischemic stroke (AIS) has not been investigated to date. In this investigation, high‐throughput sequencing was carried out to compare the circRNA expression of peripheral blood mononuclear cells (PBMCs) from five patients with AIS and five healthy subjects. A total of 521 circRNAs were expressed differentially between the patients with AIS and healthy controls (p < .05, fold difference ≥2) including 373 upregulated circRNAs and 148 downregulated circRNAs in patients with AIS compared to controls. Thirteen candidate circRNAs were verified by quantitative real‐time polymerase chain reaction (qRT‐PCR). Bioinformatics analyses showed that these differentially expressed circRNAs were highly conserved, as well as eight circRNAs that were confirmed by qRT‐PCR containing binding sites to multiple microRNAs. Kyoto Encyclopedia of Genes and Genomes pathway enrichment and gene ontology analyses indicated that the aberrantly expressed circRNAs participated in many pathophysiological processes of AIS, especially regarding inflammation and immunity. In conclusion, patients with AIS differentially express certain circRNAs in PBMCs, which may be diagnostic biomarkers or potential therapeutic targets. Taken together, the results of this study demonstrate for the first time that circular RNAs (circRNAs) are differentially expressed in the peripheral blood mononuclear cell (PBMCs) of patients with acute ischemic stroke (AIS) and may be involved in the pathogenesis of AIS. These results provide potential biomarkers for the diagnosis of AIS and suggest that it is possible to explore therapeutic interventions that specifically target aberrantly expressed circRNAs.