Hsa_circ_0005519 increases IL‐13/IL‐6 by regulating hsa‐let‐7a‐5p in CD4⁺ T cells to affect asthma

Abstract

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.