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特发性肺纤维化患者支气管肺泡灌洗液中 microRNA-30a 的下调。

Downregulation of microRNA‑30a in bronchoalveolar lavage fluid from idiopathic pulmonary fibrosis patients.

机构信息

Department of Respiratory Medicine, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.

Respiratory Department, The Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai, Shandong 264000, P.R. China.

出版信息

Mol Med Rep. 2018 Dec;18(6):5799-5806. doi: 10.3892/mmr.2018.9565. Epub 2018 Oct 18.

DOI:10.3892/mmr.2018.9565
PMID:30365083
Abstract

MicroRNAs (miRs) are short, highly conserved small noncoding RNA molecules with fundamental roles in regulating gene expression. To identify miR biomarkers associated with idiopathic pulmonary fibrosis (IPF), the expression pattern of miRs in exosomes from bronchoalveolar lavage fluid (BALF) of elderly patients with IPF were evaluated. High‑throughput quantitative detection of miR expression using a microarray indicated that miR‑125b, miR‑128, miR‑21, miR‑100, miR‑140‑3p and miR‑374b were upregulated in patients with IPF, while let‑7d, miR‑103, miR‑26 and miR‑30a‑5p were downregulated. The expression level of miR‑30a‑5p was further examined, and its potential target genes were predicted using target gene prediction analysis software. A direct regulatory association was confirmed between miR‑30a‑5p and TGF‑β activated kinase 1/MAP3K7 binding protein 3 (TAB3) via a dual‑luciferase reporter assay. Overexpression of miR‑30a‑5p decreased TAB3, α‑smooth muscle actin and fibronectin expression in A549 cells with or without transforming growth factor‑β1 treatment. The decreased expression of miR‑30a in the BALF of patients with IPF, along with the consequential increase in TAB3 expression, may be a crucial factor in IPF progression.

摘要

微小 RNA(miRs)是一类短链、高度保守的非编码小分子 RNA,在调控基因表达方面发挥着重要作用。为了鉴定与特发性肺纤维化(IPF)相关的 miR 生物标志物,我们评估了来自 IPF 老年患者支气管肺泡灌洗液(BALF)外泌体中 miR 的表达模式。使用微阵列进行高通量 miR 表达定量检测表明,IPF 患者中 miR-125b、miR-128、miR-21、miR-100、miR-140-3p 和 miR-374b 上调,而 let-7d、miR-103、miR-26 和 miR-30a-5p 下调。进一步检测了 miR-30a-5p 的表达水平,并使用靶基因预测分析软件预测其潜在靶基因。通过双荧光素酶报告基因检测证实 miR-30a-5p 与 TGF-β 激活激酶 1/MAP3K7 结合蛋白 3(TAB3)之间存在直接的调节关系。在有无转化生长因子-β1 处理的情况下,miR-30a-5p 的过表达可降低 A549 细胞中 TAB3、α-平滑肌肌动蛋白和纤维连接蛋白的表达。IPF 患者 BALF 中 miR-30a 的表达下调,同时 TAB3 表达上调,可能是 IPF 进展的关键因素。

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