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微小RNA作为肺部疾病的治疗靶点:前景与挑战

MicroRNAs as Therapeutic Targets in Lung Disease: Prospects and Challenges.

作者信息

Sato Tadashi, Baskoro Hario, Rennard Stephen I, Seyama Kuniaki, Takahashi Kazuhisa

机构信息

Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Pulmonary, Critical Care, Sleep and Allergy Medicine, Department of Internal Medicine, University of Nebraska Medical Center, Omaha.

出版信息

Chronic Obstr Pulm Dis. 2015 Dec 14;3(1):382-388. doi: 10.15326/jcopdf.3.1.2015.0160.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that regulate multiple target genes providing fine-tuned coordinated expression. Growing evidence suggests that miRNAs play important roles in lung development and the pathogenesis of lung disease and that they have great potential as novel therapeutic targets for the treatment of diseases such as lung cancer, asthma, pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD). We have previously shown that miR-146a is a promising therapeutic target for controlling abnormal inflammatory response in COPD through a series of experiments in lung fibroblasts. However, further investigations in experimental models are needed to explore the role of miR-146a in the pathogenesis and therapy of COPD. Recently, miRNAs encapsulated in extracellular vesicles (EVs) have been recognized as modulators of intercellular communication. EVs, therefore, may also have therapeutic potential and show promise for use as biomarkers for various lung diseases. In addition to miRNAs, we briefly discuss a specific long non-coding RNA (lncRNA) that may contribute to the pathogenesis of COPD. The application of miRNA-based therapeutics faces several challenges related to mode of delivery, stability, and tissue specificity. However, recent advances in nanotechnology are expected to prove valuable for the development of miRNA-based therapeutics to treat lung disease.

摘要

微小RNA(miRNA)是一类小的非编码RNA,可调控多个靶基因,实现精细协调的表达。越来越多的证据表明,miRNA在肺发育和肺部疾病发病机制中发挥重要作用,并且作为肺癌、哮喘、肺纤维化和慢性阻塞性肺疾病(COPD)等疾病的新型治疗靶点具有巨大潜力。我们之前通过在肺成纤维细胞中的一系列实验表明,miR-146a是控制COPD异常炎症反应的一个有前景的治疗靶点。然而,需要在实验模型中进一步研究,以探索miR-146a在COPD发病机制和治疗中的作用。最近,包裹在细胞外囊泡(EV)中的miRNA被认为是细胞间通讯的调节因子。因此,EV也可能具有治疗潜力,并有望用作各种肺部疾病的生物标志物。除了miRNA,我们还简要讨论了一种可能与COPD发病机制有关的特定长链非编码RNA(lncRNA)。基于miRNA的治疗方法的应用面临着与给药方式、稳定性和组织特异性相关的几个挑战。然而,纳米技术的最新进展有望为开发基于miRNA的肺部疾病治疗方法提供有价值的帮助。

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