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.
基金:
National Natural Science Foundation of China [9174210099]
第一作者单位:[1]Huazhong Univ Sci & Technol,Tongji Med Coll,Key Cite Natl Clin Res Ctr Resp Dis,Tongji Hosp,Dept Resp & Crit Care Med,Key Lab Pulm Dis Hlth M,Wuhan,Hubei,Peoples R China
通讯作者:
通讯机构:[1]Huazhong Univ Sci & Technol,Tongji Med Coll,Key Cite Natl Clin Res Ctr Resp Dis,Tongji Hosp,Dept Resp & Crit Care Med,Key Lab Pulm Dis Hlth M,Wuhan,Hubei,Peoples R China[*1]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Dept Resp Dis,1095 Jiefang Dadao Rd,Wuhan 430030,Hubei,Peoples R China
推荐引用方式(GB/T 7714):
Huang Zhenli,Cao Yong,Zhou Min,et al.Hsa_circ_0005519 increases IL-13/IL-6 by regulating hsa-let-7a-5p in CD4+ T cells to affect asthma[J].CLINICAL AND EXPERIMENTAL ALLERGY.2019,49(8):1116-1127.doi:10.1111/cea.13445.
APA:
Huang, Zhenli,Cao, Yong,Zhou, Min,Qi, Xuefei,Fu, Bohua...&Xiong, Weining.(2019).Hsa_circ_0005519 increases IL-13/IL-6 by regulating hsa-let-7a-5p in CD4+ T cells to affect asthma.CLINICAL AND EXPERIMENTAL ALLERGY,49,(8)
MLA:
Huang, Zhenli,et al."Hsa_circ_0005519 increases IL-13/IL-6 by regulating hsa-let-7a-5p in CD4+ T cells to affect asthma".CLINICAL AND EXPERIMENTAL ALLERGY 49..8(2019):1116-1127