Regulation of CBL and ESR1 expression by microRNA-22‑3p, 513a-5p and 625-5p may impact the pathogenesis of dust mite-induced pediatric asthma.
Regulation of CBL and ESR1 expression by microRNA-22‑3p, 513a-5p and 625-5p may impact the pathogenesis of dust mite-induced pediatric asthma.
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DOI：
10.3892/ijmm.2016.2634
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发表时间：
2016-08
影响因子：
5.4
通讯作者：
Zhong N
中科院分区：
文献类型：
--
作者：
Dong X;Xu M;Ren Z;Gu J;Lu M;Lu Q;Zhong N
尽管有证据表明microRNAs（miRNAs或miRs）参与了儿童哮喘，但其机制尚未完全阐明。我们的目的是鉴定新的miRNAs，并研究它们在尘螨诱导的哮喘儿童中的致病作用，以便更好地了解这种疾病的潜在机制。为此，招募了62名哮喘患者以及62名年龄和性别匹配的健康对照。使用miRCURY LNA™阵列对12对受试者随机进行基于微阵列的发现分析。使用RT-qPCR验证miRNA及其靶向信使RNA的差异表达。使用酶联免疫吸附测定（ELISA）试剂盒测定细胞因子的血浆浓度。结果显示，与对照组相比，三种新的miRNAs - miR-22- 3 p、miR-513 a-5 p和miR-625- 5 p在哮喘组中表达显著下调（p<0.01），而Cbl原癌基因、E3泛素蛋白连接酶（CBL）、过氧化物酶体增殖物激活受体γ、辅激活因子1 β的转录水平这些miRNAs靶向的雌激素受体1（ESR 1）和雌激素受体（PPARGC 1B）的表达增加（p<0.01）。两组患者血浆γ-干扰素、肿瘤坏死因子-α、白细胞介素（IL）-12和IL-10浓度比较差异有统计学意义（p<0.05）。因此，miR-513 a-5 p、miR-22- 3 p和miR-625- 5 p可能通过调节其靶基因CBL、PPARGC 1B和ESR 1对免疫应答和炎性细胞因子途径的调节产生影响，这可能导致尘螨诱导的哮喘发作。我们的发现可能为儿童哮喘的发病机制提供新的见解。
Despite evidence for the involvement of microRNAs (miRNAs or miRs) in pediatric asthma, the mechanism responsible has not yet been fully elucidated. We aimed to identify novel miRNAs and to study their pathogenic role(s) in children with dust mite-induced asthma in order to gain a better understanding of the underlying mechanism responsible for this disease. For this purpose, 62 patients with asthma as well as 62 age- and gender-matched healthy controls were recruited. Twelve pairs of subjects were randomly subjected to microarray-based discovery analysis using a miRCURY LNA™ array. The differential expression of miRNAs and their targeted messenger RNAs were validated using RT-qPCR. Plasma concentrations of cytokines were determined using an enzyme-linked immunosorbent assay (ELISA) kit. The results revealed that three novel miRNAs - miR-22-3p, miR-513a-5p and miR-625-5p - were significantly downregulated in the asthma group compared with the control group (p<0.01), whereas the transcript levels of Cbl proto-oncogene, E3 ubiquitin protein ligase (CBL), peroxisome proliferator-activated receptor gamma, coactivator 1 beta (PPARGC1B), and estrogen receptor 1 (ESR1) that are targeted by these miRNAs were increased (p<0.01). There were significant differences in the plasma concentrations of γ-interferon, tumor necrosis factor-α, interleukin (IL)-12 and IL-10 between the two groups (p<0.05). Thus, miR-513a-5p, miR-22-3p and miR-625-5p may have an impact on the regulation of the immune response and inflammatory cytokine pathways through the regulation of their target gene(s), CBL, PPARGC1B and ESR1, which may then lead to a dust mite-induced asthma attack. Our findings may provide novel insights into the pathogenesis of pediatric asthma.