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Hsa_circ_0005519 increases IL-13/IL-6 by regulating hsa-let-7a-5p in CD4+ T cells to affect asthma
Zhenli Huang1, Yong Cao1, Min Zhou1
1Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Key Cite of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, Wuhan, China.
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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