Chinese Journal of Evidence-Based Pediatrics ›› 2021, Vol. 16 ›› Issue (1): 66-70.DOI: 10.3969/j.issn.1673-5501.2021.01.006

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The expression and function analysis of circHIPK3 in children with asthma

LIANG Qiuyan1a, ZHENG Hongmei1b, FU Jinrong1c, LIU Lijuan1b, ZHANG Xiaobo1b, QIAN Liling1b, ZHOU Yufeng1a,2   

  1. 1 Children's Hospital of Fudan University, Shanghai 201102, China; a Institute of Pediatrics, b Department of Respiratory Medicine, c Department of General Medicine;
    2 Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
  • Received:2021-01-11 Revised:2021-02-13 Online:2021-02-25 Published:2021-03-22
  • Contact: ZHOU Yufeng, email: yfzhou1@fudan.edu.cn

Abstract: Background CircRNAs play an important part in various dieases. But circRNAs in pediatric asthma have not been reported so far. It had been reported that circHIPK3 promoted Th2 differentiation in allergic rhinitis. Objective To explore the expression and potential function of circHIPK3 in children with asthma. Design The study developed by firstly collecting peripheral blood mononuclear cells (PBMCs) from asthmatic patients and healthy controls. The expression of circHIPK3 was detected and the correlations between circHIPK3 and T cell's transcription factors were analyzed. Relative results were validated in asthma mice. Sequently, bioinformatics analysis was used to analyze possible mechanisms and correlation analysis was performed between circHIPK3 and clinical indicators. Methods Peripheral blood mononuclear cells (PBMCs) were collected from asthmatic patients and healthy controls from August 26,2017 to August 5,2019 in the outpatient respirology clinic at Children's Hospital of Fudan University.qRT-PCR was used for the detection of the expression of circHIPK3 and T-bet in the PBMCs.Pearson correlation analysis was used to analyze the correlation between circHIPK3 and T-bet.A cockroach extract (CRE)-induced asthma model was adopted in the experiment. The expression of circHIPK3 and T-bet in the mice lung were detected by qRT-PCR. Bioinformatics analysis was used to explore the potential mechanism between circHIPK3 and T-bet in children with asthma. Pearson correlation analysis was used to analyze the correlation between circHIPK3 and eosinophils in peripheral blood. Main outcome measures The main outcome measures were relative expression of circHIPK3 and T-bet, as well as the correlation coefficients between them. Results A total of 43 patients of mild asthma (35 males, median age 6.5 years) and 28 normal controls (22 males, median age 6.4 years) were evaluated. Comparing with healthy controls,the expression of circHIPK3 (t=4.627,P<0.001) and T-bet (t=2.727, P<0.01) were significantly decreased in asthmatic patients.circHIPK3 was positively correlated with T-bet in pediatric asthma patients (R=0.483 0, P=0.000 7). The results in lung remodeling in asthma mice were in accordance with those in human PBMCs. miR-485-3p was up-regulated in children with asthma by analysis of a reported GEO database. circHIPK3 could bind with miR-485-3p in a sponge way. T-bet was a predicted target of miR-485-3p. A negative correlation was detected between circHIPK3 and eosinophils in peripheral blood (R=-0.369 2, P=0.019 1). Conclusion circHIPK3 was down-regulated in the asthmatic patients and mice, potentially regulating T-bet through sponge miR-485-3p.

Key words: Circular RNAs, Asthma, T cell differentiation