MicroRNAs as Therapeutic Targets in Lung Disease: Prospects and Challenges

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 in vitro experiments in lung fibroblasts. However, further investigations in in vivo 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.

Keywords: chronic obstructive pulmonary disease; extracellular vesicles; long non-coding RNA; lung diseases; miRNA-based therapeutics; microRNA.

Grants and funding

This work was supported by Grant-in-Aid for Scientific Research (T.S., 26461199) and the Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine (T.S.).