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

• Published in: Clinical and experimental allergy Vol. 49; no. 8; pp. 1116 - 1127
• Main Authors: Huang, Zhenli, Cao, Yong, Zhou, Min, Qi, Xuefei, Fu, Bohua, Mou, Yong, Wu, Guorao, Xie, Jungang, Zhao, Jianping, Xiong, Weining
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.08.2019
• Subjects: Asthma; Biomarkers; CD4 antigen; CD4+ T cells; hsa_circ_0005519; hsa‐let‐7a‐5p; Inflammation; Leukocytes (eosinophilic); Lymphocytes; Lymphocytes T; mRNA; Nitric oxide; Patients; PBMCs; Peripheral blood; asthma; CD4+ T cells; hsa-let-7a-5p; PBMCs; hsa_circ_0005519
• DOI: 10.1111/cea.13445
• ISSN: 0954-7894; 1365-2222

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.