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  • 董善武,陈咏丽,陈玲,何春枝,王震宇.长链非编码RNA INK4位点反义非编码RNA与微RNA-125a在支气管哮喘患儿血浆中的表达及临床意义[J].第二军医大学学报,2020,41(5):540-545    [点击复制]
  • DONG Shan-wu,CHEN Yong-li,CHEN Ling,HE Chun-zhi,WANG Zhen-yu.Expression and clinical significance of long non-coding RNA antisense non-coding RNA in the INK4 locus and microRNA-125a in plasma of children with bronchial asthma[J].Acad J Sec Mil Med Univ,2020,41(5):540-545   [点击复制]
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长链非编码RNA INK4位点反义非编码RNA与微RNA-125a在支气管哮喘患儿血浆中的表达及临床意义
董善武1*,陈咏丽1,陈玲1,何春枝1,王震宇2
0
(1. 武汉市第四医院, 华中科技大学同济医学院附属普爱医院儿科, 武汉 430034;
2. 武汉科技大学医学院基础医学院生物化学与分子生物学系, 武汉 430065
*通信作者)
摘要:
目的 探讨lncRNA INK4位点反义非编码RNA (ANRIL)在支气管哮喘患儿血浆中的表达及其与患病风险、疾病严重程度和miRNA-125a的关系。方法 连续纳入急性发作期支气管哮喘患儿、缓解期支气管哮喘患儿和匹配的健康儿童各70例,收集受试者实验室检查及肺通气功能检测结果。采用qRT-PCR检测受试者血浆中lncRNA ANRIL和miRNA-125a表达水平,并用ELISA法检测受试者血浆中炎性因子(TNF-α、IL-1β、IL-6和IL-17)水平。结果 LncRNA ANRIL在急性发作期支气管哮喘患儿血浆中的表达水平高于缓解期支气管哮喘患儿和健康儿童(P均<0.001),在缓解期支气管哮喘患儿血浆中的表达水平高于健康儿童(P=0.002)。ROC曲线表明lncRNA ANRIL能很好地区分3组受试者。LncRNA ANRIL表达水平与急性发作期支气管哮喘患儿疾病严重程度有关(P=0.001),与TNF-α、IL-1β、IL-6、IL-17表达水平均呈正相关(P均<0.05),而与第1秒用力呼气容积(FEV1)/用力肺活量(FVC)、FEV1占预计值的百分比(FEV1% Pred)均呈负相关(P均<0.05)。LncRNA ANRIL表达水平与缓解期支气管哮喘患儿TNF-α、IL-1β和IL-17表达水平及健康儿童IL-6表达水平均呈正相关(P均<0.05)。同时,lncRNA ANRIL表达水平还与3组受试者miRNA-125a表达水平均呈负相关(P均<0.05),并且miRNA-125a表达水平与急性发作期支气管哮喘患儿FEV1/FVC、FEV1% Pred均呈正相关(P均<0.001)。结论 LncRNA ANRIL对儿童支气管哮喘及急性发作有诊断价值,对哮喘严重程度和患儿炎症水平有潜在的预测价值;lncRNA ANRIL可能通过靶向调控miRNA-125a参与儿童支气管哮喘的发生、发展。
关键词:  哮喘  儿童  长链非编码RNA ANRIL  微RNA-125a  炎性因子
DOI:10.16781/j.0258-879x.2020.05.0540
投稿时间:2019-10-29修订日期:2019-12-23
基金项目:湖北省卫生健康委员会基金(WJ2019M020).
Expression and clinical significance of long non-coding RNA antisense non-coding RNA in the INK4 locus and microRNA-125a in plasma of children with bronchial asthma
DONG Shan-wu1*,CHEN Yong-li1,CHEN Ling1,HE Chun-zhi1,WANG Zhen-yu2
(1. Department of Paediatrics, Wuhan Fourth Hospital(Puai Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430034, Hubei, China;
2. Department of Biochemistry and Molecular Biology, Basic Medical College, School of Medcine, Wuhan University of Science and Technology, Wuhan 430065, Hubei, China
*Corresponding author)
Abstract:
Objective To evaluate the correlation of long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) with disease risk and severity of bronchial asthma as well as plasma microRNA (miRNA)-125a expression in child patients. Methods Seventy children with asthma exacerbation, 70 children with asthma remission and 70 matched healthy controls were consecutively enrolled in this study. Laboratory parameters and lung function indexes of the participants were recorded. LncRNA ANRIL and miRNA-125a expression levels in plasma were determined using qRT-PCR. Tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and IL-17 levels in plasma were determined using enzyme-linked immunosorbent assay (ELISA). Results LncRNA ANRIL expression was the highest in the asthma exacerbation children, followed by asthma remission children and healthy controls. There were significant differences in the expression of lncRNA ANRIL among the three groups (all P<0.01). Receiver operating characteristic curves revealed that lncRNA ANRIL could well differentiate the participants in the three groups. In the children with asthma exacerbation, lncRNA ANRIL expression was associated with disease severity (P=0.001), positively associated with the levels of TNF-α, IL-1β, IL-6 and IL-17 (all P<0.05), while negatively associated with forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) and FEV1 as percentage of predicted (FEV1%Pred) value (both P<0.05). LncRNA ANRIL expression was also positively associated with the levels of TNF-α, IL-1β and IL-17 in the asthma remission children and IL-6 level in healthy controls (all P<0.05). LncRNA ANRIL expression was negatively associated with miRNA-125a expression in all the participants (all P<0.05). Besides, miRNA-125a expression was positively correlated with FEV1/FVC and FEV1%Pred value in the children with asthma exacerbetion (both P<0.001). Conclusion LncRNA ANRIL may serve as a novel biomarker for predicting asthma, asthma acute exacerbation and severity, and inflammation level. It may participate in the development and progression of asthma in children via targeting miRNA-125a.
Key words:  asthma  children  long non-coding RNA ANRIL  microRNA-125a  inflammatory cytokines