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

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 hsalet-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. K E Y W O R D Sasthma, CD4 + T cells, hsa_circ_0005519, hsa-let-7a-5p, PBMCs

A comprehensive analysis of microRNAs as diagnostic biomarkers for asthma

“…According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard, 47 the standard literature selection process was conducted as shown in Figure 1. We finally included 72 articles 21,22,[25][26][27][28][29][30][31] with 4143 patients and 2188 controls based on the inclusion and exclusion criteria. The features of the included research are presented in Table 1.…”

“…Furthermore, the decrease of let-7a-5p in asthma was associated with peripheral blood eosinophil ratio. 22 Compared with non-asthmatics and mild-tomoderate asthmatics, plasma miR-155 level was significantly elevated in patients with severe asthma. 23 Besides, the increased expression of miR-146 was known to inhibit the nuclear factorkappa B factor (NF-κB), this limiting to inflammatory responses in plasma from asthma.…”

The emerging landscape of circular RNAs in immunity: breakthroughs and challenges

“…Circ_0005519 expressions between CD4 + T cells and PBMCs were harmonious in asthmatic cases. From the mechanistical perspective, circ_0005519 might bind to hsa-let-7a-5p and mitigate inhabitation for IL-13/IL-6 in CD4 + T cells [50].…”

Circular RNA and tumor microenvironment

“…CircRNAs regulate the T cell-mediated immune response, which is critical for tumor immunity. Correlation assays revealed that hsa_circ_0005519 activated the A circRNAs sponge miRNA to release mRNA and regulate transcription indirectly; B circRNAs with RNA-binding protein-binding motifs sponge or decoy RNA binding proteins (RBPs) to regulate transcription; C circRNAs serve as a scaffold for proteins; D circRNAs with internal ribosome entry sites (IRESs) can be translated into peptides or proteins, driven by m6A; E circRNAs regulate transcription of parental genes immune response, as it might induce cytokine IL-13 and IL-6 expression by regulating hsa-let-7a-5p in CD4+ T cells [43]. CircRNA hsa_circ_0012919 contributed to DNA methylation of CD70, a member of the TNF family, by sponging DNA methylation-related miRNAs in CD4+ T cells [44].…”