miR-145-5p 通过靶向 Smad3 调节鼻息肉的上皮-间充质转化。

IF 2.9 3区 医学 Q1 OTORHINOLARYNGOLOGY
Mengyu Zhang, Xiaole Peng, Xiaolong Liang, Wentao Wang, Yuqing Yang, Fan Xu, Xiaomin Lu, Dechun Geng, Manyi Li
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引用次数: 0

摘要

目的:慢性鼻炎(CRS)的发病率呈逐年上升趋势,由于缺乏有效的治疗方法,给患者和社会都带来了沉重的负担。CRS 患者鼻息肉的形成主要与组织重塑有关,而组织重塑主要受上皮间质转化(EMT)的影响。微RNA(miRNA)通过miRNA mRNA调控网络在多种疾病的发病机制中发挥着关键作用,但miRNA参与鼻息肉形成的具体机制尚不清楚:方法:采用Western印迹、定量实时聚合酶链反应(qRT-PCR)、免疫组织化学、免疫荧光染色等方法检测EMT标记物和Smad3的表达。通过基因表达总库(GEO)筛选鼻息肉和正常组织中的差异表达基因。为了预测 miR 145 5p 的靶基因,使用了三个不同的 miRNA 靶基因预测数据库。结果发现:miR 145 5p 与鼻息肉组织的 EMT 过程有关,并在鼻息肉组织中被显著下调。在体外实验中,我们发现 miR 145 5p 下调会促进 EMT。miR 145 5p 水平的升高逆转了转化生长因子β1(TGF β1)诱导的 EMT。生物信息学发现,miR 145 5p 与 Smad3 存在靶向关系。通过进一步实验证明,miR 145 5p 具有抑制 Smad3 表达的作用:总之,miR 145 5p 是一个有希望抑制鼻息肉形成的靶点,为纳米粒子介导的 miR 145 5p 递送治疗鼻息肉提供了理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MicroRNA-145-5p Regulates the Epithelial-Mesenchymal Transition in Nasal Polyps by Targeting Smad3.

Objectives: The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear.

Methods: The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays.

Results: miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression.

Conclusion: Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.

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来源期刊
CiteScore
4.90
自引率
6.70%
发文量
49
审稿时长
6-12 weeks
期刊介绍: Clinical and Experimental Otorhinolaryngology (Clin Exp Otorhinolaryngol, CEO) is an international peer-reviewed journal on recent developments in diagnosis and treatment of otorhinolaryngology-head and neck surgery and dedicated to the advancement of patient care in ear, nose, throat, head, and neck disorders. This journal publishes original articles relating to both clinical and basic researches, reviews, and clinical trials, encompassing the whole topics of otorhinolaryngology-head and neck surgery. CEO was first issued in 2008 and this journal is published in English four times (the last day of February, May, August, and November) per year by the Korean Society of Otorhinolaryngology-Head and Neck Surgery. The Journal aims at publishing evidence-based, scientifically written articles from different disciplines of otorhinolaryngology field. The readership contains clinical/basic research into current practice in otorhinolaryngology, audiology, speech pathology, head and neck oncology, plastic and reconstructive surgery. The readers are otolaryngologists, head and neck surgeons and oncologists, audiologists, and speech pathologists.
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