The Identification of Childhood Asthma Progression-Related lncRNAs and mRNAs Suitable as Biomarkers Using Weighted Gene Coexpression Network Analysis

Hao, Min; Zan, Jinling

doi:10.1155/2021/5511507

Cited by 8 publications

(7 citation statements)

References 51 publications

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“…The effect of glutathione on the regulation of Treg/Th17 cell homeostasis through inhibition of intracellular autophagy has also been demonstrated in peripheral blood mononuclear cells (PBMCs) from patients and mouse models of AR [ 59 ]. This is consistent with our data mining results from lncRNA microarray datasets GSE65204 and GSE19187, which also identified an effect of glutathione on respiratory allergy [ 60 ]. Mast cell degranulation plays a key role in allergic responses to conditions such as asthma and AR [ 61 ].…”

Section: Discussionsupporting

confidence: 91%

Microenvironment modulation by key regulators of RNA N6-methyladenosine modification in respiratory allergic diseases

et al. 2023

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Background RNA N6-methyladenosine (m6A) regulators are considered post-transcriptional regulators that affect several biological functions, and their role in immunity, in particular, is emerging. However, the role of m6A regulators in respiratory allergic diseases remains unclear. Therefore, we aimed to investigate the role of key m6A regulators in mediating respiratory allergic diseases and immune microenvironment infiltration characteristics. Methods We downloaded gene expression profiles of respiratory allergies from the Gene Expression Omnibus (GEO) database and we performed hierarchical clustering, difference analysis, and construction of predictive models to identify hub m6A regulators that affect respiratory allergies. Next, we investigate the underlying biological mechanisms of key m6A regulators by performing PPI network analysis, functional enrichment analysis, and immune microenvironment infiltration analysis. In addition, we performed a drug sensitivity analysis on the key m6A regulator, hoping to be able to provide some implications for clinical medication. Results In this study, we identified four hub m6A regulators that affect the respiratory allergy and investigated the underlying biological mechanisms. In addition, studies on the characteristics of immune microenvironment infiltration revealed that the expression of METTL14, METTL16, and RBM15B correlated with the infiltration of the mast and Th2 cells in respiratory allergy, and METTL16 expression was found to be significantly negatively correlated with macrophages for the first time (R = -0.53, P < 0.01). Finally, a key m6A regulator, METTL14, was screened by combining multiple algorithms. In addition, by performing a drug sensitivity analysis on METTL14, we hypothesized that it may play an important role in the improvement of allergic symptoms in the upper and lower airways with topical nasal glucocorticoids. Conclusions Our findings suggest that m6A regulators, particularly METTL14, play a crucial role in the development of respiratory allergic diseases and the infiltration of immune cells. These results may provide insight into the mechanism of action of methylprednisolone in treating respiratory allergic diseases.

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Section: Discussionsupporting

confidence: 91%

Microenvironment modulation by key regulators of RNA N6-methyladenosine modification in respiratory allergic diseases

et al. 2023

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“…LncRNAs, with a length of over 200 nt, play critical roles in regulating gene expression at multiple levels, including transcriptional, post-transcriptional levels, microRNA chelation and translation efficiency regulation and more ( Hao and Zan, 2021 ; Wang et al, 2021 ). Although many studies have proved that lncRNAs and childhood asthma are inextricably linked ( Wang et al, 2021 ), the roles of lncRNAs in childhood asthma remain unclear.…”

Section: Ncrnas In the Regulation Of Childhood Asthmamentioning

confidence: 99%

“…Additionally, Treg/Th17 imbalance was also associated with childhood asthma through neutrophil recruitment and exacerbation of airway inflammation, which was mediated by upregulating Th17-type cytokines (IL-17A, IL-17F) and downregulating Treg-type cytokines (IL-10, transforming growth factor (TGF-β) and so on ( Westfall et al, 2021 ). LncRNA MEG3 regulated RORgammat expression by competitively sponge miR-17 and ultimately affected the balance of Treg/Th17 ( Qiu et al, 2019 ; Hao and Zan, 2021 ; Wang et al, 2021 ). In addition, lncRNA RP11-401.2 upregulated in eosinophils dysfunction regulated eosinophilic asthma ( Tian et al, 2018 ).…”

Section: Ncrnas In the Regulation Of Childhood Asthmamentioning

confidence: 99%

“…Nevertheless, its role in the pathogenesis of asthma remains to be further studied ( Wang et al, 2017 ). Recently, lncRNAs SNHG8 and LINC01559 have been found to be directly involved in the occurrence and progression of childhood asthma through PI3K/AKT signaling pathway ( Hao and Zan, 2021 ), and may serve as candidates for therapeutic strategies for childhood asthma ( Table 2 ). Further elucidating the role of various lncRNAs in childhood asthma will help to understand the pathogenesis of asthma and develop potential treatment targets.…”

Section: Ncrnas In the Regulation Of Childhood Asthmamentioning

confidence: 99%

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Emerging Roles of Non-Coding RNAs in Childhood Asthma

et al. 2022

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Asthma is a chronic airway inflammatory disease in children characterized by airway inflammation, airway hyperresponsiveness and airway remodeling. Childhood asthma is usually associated with allergy and atopy, unlike adult asthma, which is commonly associated with obesity, smoking, etc. The pathogenesis and diagnosis of childhood asthma also remains more challenging than adult asthma, such as many diseases showing similar symptoms may coexist and be confused with asthma. In terms of the treatment, although most childhood asthma can potentially be self-managed and controlled with drugs, approximately 5–10% of children suffer from severe uncontrolled asthma, which carries significant health and socioeconomic burdens. Therefore, it is necessary to explore the pathogenesis of childhood asthma from a new perspective. Studies have revealed that non-coding RNAs (ncRNAs) are involved in the regulation of respiratory diseases. In addition, altered expression of ncRNAs in blood, and in condensate of sputum or exhalation affects the progression of asthma via regulating immune response. In this review, we outline the regulation and pathogenesis of asthma and summarize the role of ncRNAs in childhood asthma. We also hold promise that ncRNAs may be used for the development of biomarkers and support a new therapeutic strategy for childhood asthma.

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“…Long noncoding RNAs (lncRNAs), a kind of gene transcripts with more than 200 nt in length, fail the function of encoding proteins or only encode short multi-classes of RNA molecules. LncRNAs have been considered as potential biomarkers for childhood asthma ( 7 ). There is growing evidence that lncRNAs and miRNAs act as competing endogenous RNA (ceRNAs) to inhibit each other, which form an accurate regulatory network and regulate the target genes of miRNAs ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Lncrna NEAT1 Regulates Th1/Th2 in Pediatric Asthma by Targeting MicroRNA-217/GATA3

Yan¹,

Liu²,

Li³

2023

ijph

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Background: The imbalance of immune response between helper Th1 and Th2 cells is the direct cause of asthma. It was closely related to abnormal expression of lncRNAs. However, whether lncRNAs can regulate Th1/Th2 balance in pediatric asthma remains to be investigated. Methods: Peripheral blood samples were collected from children with asthma and normal volunteers at the Children’s Hospital of Shaanxi Provincial People’s Hospital (Xi’an, China) in 2020. The qRT-PCR was used to detect the expression of lncRNA NEAT1, miR-217 and GATA3 in peripheral blood samples. The effects of lncRNA NEAT1, miR-217, and GATA3 on CD4+T cell population were detected in vitro. Meanwhile, the regulatory effect of lncRNA NEAT1/miR-217/GATA3 was evaluated through the dual luciferase report assay, functional assays and animal experiments. Results: We investigated that lncRNA NEAT1 and GATA3 was significantly up-regulated in CD4+T cells in peripheral blood of children with asthma (P<0.001). Knockdown of lncRNA NEAT1 or GATA3 significantly reduced Th2-related cytokines (P<0.05), but had no effect on Th1 cells. Importantly, the interactions of lncRNA NEAT1 with miR-217 and miR-217 with GATA3 were confirmed by dual luciferase report assay. Meanwhile, functional assays and animal experiments demonstrated that lncRNA NEAT1 regulated GATA3 expression through sponge miR-217, thereby regulating Th1/Th2 balance in CD4+T cells in pediatric asthma. Conclusion: lncRNA NEAT1/miR-217/GATA3 axis may reveal the immunological mechanism of pediatric asthma, which has potential clinical application value in the future.

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The Identification of Childhood Asthma Progression-Related lncRNAs and mRNAs Suitable as Biomarkers Using Weighted Gene Coexpression Network Analysis

Cited by 8 publications

References 51 publications

Microenvironment modulation by key regulators of RNA N6-methyladenosine modification in respiratory allergic diseases

Microenvironment modulation by key regulators of RNA N6-methyladenosine modification in respiratory allergic diseases

Emerging Roles of Non-Coding RNAs in Childhood Asthma

Lncrna NEAT1 Regulates Th1/Th2 in Pediatric Asthma by Targeting MicroRNA-217/GATA3

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