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Article Abstract
Background: Circular RNAs (circRNAs) are a class of non-coding RNAs that could serve as novel biomarkers for the diagnosis and treatment of diseases. We hypothesized that circRNAs of CD4 T cells are involved in asthma.
Objective: In this study, we investigated the circRNA expression profile and the possible mechanism by which hsa_circ_0005519 participates in asthma.
Methods: The expression profiles of circRNAs in CD4 T cells were revealed by circRNA microarray. Hsa_circ_0005519 expression in CD4 T cells was confirmed in asthmatic patients (n = 65) and healthy subjects (n = 30). Hsa-let-7a-5p, the target of hsa_circ_0005519, was predicted by online algorithms and verified by a dual-luciferase reporter assay. Correlation assays between the expression of hsa_circ_0005519 and hsa-let-7a-5p, the mRNA levels of interleukin (IL)-13 and IL-6 in CD4 T cells, and the clinical characteristics of asthmatic patients were performed. The role of hsa_circ_0005519 in proinflammatory cytokine expression was investigated in CD4 T cells from asthmatic patients in vitro. Hsa_circ_0005519 expression in PBMCs was determined in another cohort including 30 asthmatic patients and 24 controls. Correlation assays of hsa_circ_0005519 expressions between CD4 T cells and PBMCs were performed.
Results: Hsa_circ_0005519 was up-regulated and negatively correlated with hsa-let-7a-5p expression in CD4 T cells of asthmatic patients. Both the fraction of exhaled nitric oxide (FeNO) and the peripheral blood eosinophil ratio were positively correlated with hsa_circ_0005519 expression in CD4 T cells. These outcomes were also different in asthmatic patients with low vs high hsa_circ_0005519 levels. Hsa_circ_0005519 expressions between CD4 T cells and PBMCs were concordant in asthmatic patients. Mechanistically, hsa_circ_0005519 might bind to hsa-let-7a-5p and relieve suppression for IL-13/IL-6 in CD4 T cells.
Conclusions And Clinical Relevance: Our data suggest that hsa_circ_0005519 may induce IL-13 and IL-6 expression by regulating hsa-let-7a-5p in CD4 T cells to affect asthma. And hsa_circ_0005519 may be a potential biomarker of asthma.
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