Middle Ear microRNAs Drive Mucin Gene Response

IF 2 3区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Laryngoscope Pub Date : 2024-11-21 DOI:10.1002/lary.31912

Gabriel Nahas MS, Yajun Chen MD, Apurva Ningundi BS, Samuel Tercyak BS, Diego Preciado MD, PhD

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Abstract

Objective(s)

To investigate the role of microRNA-378 (miR-378) in the regulation of mucin gene expression and inflammatory response in human middle ear epithelial cells (HMEEC) during bacterial infection by non-typeable Haemophilus influenzae (NTHi).

Methods

Human middle ear epithelial cells (HMEEC) were cultured and transfected with miR-378 or control miRNA. Post-transfection, cells were exposed to NTHi lysates. mRNA levels of MUC5B, MUC5AC, and IL-8 were quantified using RT-qPCR, and promoter activity was measured via luciferase assays. The effects of miR-378 on mucin and cytokine gene expression were analyzed.

Results

Transfection with miR-378 significantly increased the expression of MUC5B (3.6 fold, p < 0.01), MUC5AC (19.1 fold, p < 0.01), and IL-8 (2.01 fold, p < 0.05) in HMEEC. NTHi exposure reduced MUC5B (1.385 fold, p < 0.05) and MUC5AC (1.61 fold, p < 0.05) gene expression in miR-378 transfected cells but significantly increased IL-8 levels (1.32 fold, p < 0.05). Luciferase assays showed that miR-378 upregulated the promoter activity of MUC5B (1.4 fold, p < 0.01) and MUC5AC (1.6 fold, p < 0.01) genes, indicating its role in transcriptional regulation.

Conclusion

miR-378 plays a crucial role in promoting mucin overproduction and an inflammatory response in the middle ear epithelium during OM. Targeting miR-378 could offer a novel therapeutic strategy for preventing the progression from AOM to COM.

Level of Evidence

NA Laryngoscope, 135:1815–1820, 2025

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中耳 microRNA 驱动粘蛋白基因反应

目的方法：培养人中耳上皮细胞（HMEEC）并转染 miR-378 或对照 miRNA。用 RT-qPCR 定量 MUC5B、MUC5AC 和 IL-8 的 mRNA 水平，用荧光素酶测定启动子活性。分析了 miR-378 对粘蛋白和细胞因子基因表达的影响：结果：转染 miR-378 能显著增加 MUC5B 的表达（3.6 倍，p 结论：在 OM 期间，miR-378 在促进中耳上皮粘蛋白过度分泌和炎症反应方面起着至关重要的作用。以 miR-378 为靶点可提供一种新的治疗策略，防止 AOM 演变为 COM。

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来源期刊

Laryngoscope 医学-耳鼻喉科学

CiteScore

6.50

自引率

7.70%

发文量

500

审稿时长

2-4 weeks

期刊介绍： The Laryngoscope has been the leading source of information on advances in the diagnosis and treatment of head and neck disorders since 1890. The Laryngoscope is the first choice among otolaryngologists for publication of their important findings and techniques. Each monthly issue of The Laryngoscope features peer-reviewed medical, clinical, and research contributions in general otolaryngology, allergy/rhinology, otology/neurotology, laryngology/bronchoesophagology, head and neck surgery, sleep medicine, pediatric otolaryngology, facial plastics and reconstructive surgery, oncology, and communicative disorders. Contributions include papers and posters presented at the Annual and Section Meetings of the Triological Society, as well as independent papers, "How I Do It", "Triological Best Practice" articles, and contemporary reviews. Theses authored by the Triological Society’s new Fellows as well as papers presented at meetings of the American Laryngological Association are published in The Laryngoscope. • Broncho-esophagology • Communicative disorders • Head and neck surgery • Plastic and reconstructive facial surgery • Oncology • Speech and hearing defects