Small extracellular vesicles facilitate epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps via the miR-375-3p/QKI axis.

IF 4.8 2区医学 Q1 OTORHINOLARYNGOLOGY

Rhinology Pub Date : 2024-08-01 DOI:10.4193/Rhin23.520

X Wang, R Zheng, W Liang, H Qiu, T Yuan, W Wang, H Deng, W Kong, J Chen, Y Bai, Y Li, Y Chen, Q Wu, S Wu, X Huang, Z Shi, Q Fu, Y Zhang, Q Yang

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引用次数: 0

Abstract

Background: Epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the involvement of small extracellular vesicles (sEVs) in EMT and their contributions to CRSwNP has not been extensively investigated.

Methods: SEVs were isolated from nasal mucosa through ultracentrifugation. MicroRNA sequencing and reverse-transcription quantitative polymerase chain reaction were employed to analyze the differential expression of microRNAs carried by sEVs. Human nasal epithelial cells (hNECs) were used to assess the EMT-inducing effect of sEVs/microRNAs. EMT-associated markers were detected by western blotting and immunofluorescence. Dual-luciferase reporter assay was performed to determine the target gene of miR-375-3p. MicroRNA mimic, lentiviral, and plasmid transduction were used for functional experiments.

Results: In line with the greater EMT status in eosinophilic CRSwNP (ENP), sEVs derived from ENP (ENP-sEVs) could induce EMT in hNECs. MiR-375-3p was elevated in ENP-sEVs compared to that in control and nonENP. MiR-375-3p carried by ENP-sEVs facilitated EMT by directly targeting KH domain containing RNA binding (QKI) at seed sequences of 913-919, 1025-1033, and 2438-2444 in 3â€™-untranslated region. Inhibition of QKI by miR-375-3p overexpression promoted EMT, which could be reversed by restoration of QKI. Furthermore, the abundance of miR-375-3p in sEVs was closely correlated with the clinical symptom score and disease severity.

Conclusions: MiR-375-3p-enriched sEVs facilitated EMT by suppressing QKI in hNECs. The association of miR-375-3p with disease severity underscores its potential as both a diagnostic marker and a therapeutic target for the innovative management of CRSwNP.

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小细胞外囊泡通过 miR-375-3p/QKI 轴促进慢性鼻炎伴鼻息肉的上皮-间质转化。

背景：上皮-间质转化（EMT）在慢性鼻炎伴鼻息肉（CRSwNP）的发病机制中起着至关重要的作用。然而，关于小细胞外囊泡（sEVs）参与上皮-间质转化及其对慢性鼻炎伴鼻息肉（CRSwNP）的贡献，尚未进行广泛研究：方法：通过超速离心从鼻粘膜中分离出 SEVs。方法：通过超速离心从鼻粘膜中分离出 SEVs，采用微RNA测序和反转录定量聚合酶链反应分析 sEVs 所携带的微RNA的差异表达。用人鼻上皮细胞（hNECs）来评估 sEVs/microRNAs 的 EMT 诱导效应。EMT相关标记物通过免疫印迹和免疫荧光进行检测。进行双荧光素酶报告实验以确定 miR-375-3p 的靶基因。微RNA模拟物、慢病毒和质粒转导用于功能实验：结果：与嗜酸性细胞 CRSwNP（ENP）的 EMT 状态一致，来自 ENP 的 sEVs（ENP-sEVs）可诱导 hNECs 的 EMT。与对照组和非ENP相比，ENP-sEVs中的MiR-375-3p升高。ENP-sEVs携带的MiR-375- 3p通过直接靶向3'-非翻译区913-919、1025-1033和2438-2444种子序列上的含KH结构域的RNA结合（QKI）来促进EMT。miR-375-3p 过表达抑制 QKI 会促进 EMT，而恢复 QKI 则可逆转 EMT。此外，sEVs 中 miR-375-3p 的丰度与临床症状评分和疾病严重程度密切相关：结论：富含 miR-375-3p 的 sEVs 通过抑制 QKI 促进了 hNECs 的 EMT。miR-375-3p与疾病严重程度的关联突显了其作为诊断标志物和治疗靶点的潜力，可用于CRSwNP的创新治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Rhinology 医学-耳鼻喉科学

CiteScore

15.80

自引率

9.70%

发文量

135

审稿时长

6-12 weeks

期刊介绍： Rhinology serves as the official Journal of the International Rhinologic Society and is recognized as one of the journals of the European Rhinologic Society. It offers a prominent platform for disseminating rhinologic research, reviews, position papers, task force reports, and guidelines to an international scientific audience. The journal also boasts the prestigious European Position Paper in Rhinosinusitis (EPOS), a highly influential publication first released in 2005 and subsequently updated in 2007, 2012, and most recently in 2020. Employing a double-blind peer review system, Rhinology welcomes original articles, review articles, and letters to the editor.