lncRNA DANCR通过抑制miR-338-3p增强过敏性鼻炎的炎症反应

文献信息

中文摘要

目的： 长链非编码RNA（lncRNAs）已被认为与过敏性鼻炎（AR）的发生发展有关。本研究旨在探讨lncRNA DANCR在AR中的临床意义和功能机制。方法：招募志愿者参与者，包括健康对照者和AR患者，收集临床信息和血清样本。通过qRT-PCR定量DANCR和miR-338-3p的表达。使用IL-13刺激的人鼻上皮细胞（HNECs）建立AR体外模型，并通过分子转染调节靶基因表达。采用ELISA检测IL-4、IL-5、eotaxin和GM-CSF水平。分别通过CCK8和流式细胞术评估细胞活力和凋亡。使用双荧光素酶报告系统验证DANCR与miR-338-3p之间的相互作用。结果：AR患者血清DANCR表达显著升高，显示出高诊断准确性（AUC = 0.878），敏感性为82.05%，特异性为81.25%。IL-13刺激增加了HNECs中的DANCR。IL-13诱导HNECs导致炎症增加、细胞活力降低和凋亡过程调节；然而，沉默DANCR减轻了这些IL-13介导的效应。在AR和IL-13诱导的HNECs中，miR-338-3p降低，而DANCR作为其ceRNA发挥作用。沉默miR-338-3p逆转了DANCR下调的保护作用。结论：在本研究中，观察到AR中DANCR表达升高与疾病进展密切相关。此外，揭示了其通过miR-338-3p调节炎症反应和细胞功能的作用方式。

英文摘要

ObjectiveLong non-coding RNAs (lncRNAs) have been implicated in the development of allergic rhinitis (AR). This study aimed to examine the clinical importance and functional mechanism of lncRNA DANCR in AR.MethodsVolunteer participants, including healthy controls and those with AR, were recruited, with clinical information and serum samples being gathered. Expression of DANCR and miR-338-3p was quantified by qRT-PCR. An in vitro model of AR was established using IL-13-stimulated human nasal epithelial cells (HNECs), and modulation of target expression via molecular transfection was regulated. ELISA was used to measure IL-4, IL-5, eotaxin, and GM-CSF levels. Cell viability and apoptosis were assessed by CCK8 and flow cytometry, respectively. The interaction between DANCR and miR-338-3p was validated using a dual luciferase reporter system.ResultsSerum DANCR expression was significantly elevated in AR patients, showing high diagnostic accuracy (AUC = 0.878) with 82.05% sensitivity and 81.25% specificity. IL-13 stimulation increased DANCR in HNECs. IL-13 induction in HNECs led to an increase in inflammation, a decrease in cell viability, and modulation of apoptotic processes; however, silencing DANCR mitigated these IL-13-mediated effects. In AR and IL-13-induced HNECs, miR-338-3p was decreased, while DANCR functioned as its ceRNA. miR-338-3p silencing reversed the protective effects of DANCR downregulation.ConclusionIn this research, it was observed that elevated DANCR expression in AR was tightly linked to disease progression. Furthermore, it uncovered its mode of action in modulating inflammatory responses and cellular functions via miR-338-3p.