Emerging Role of MicroRNAs and Long Noncoding RNAs in Respiratory Disease

The advent of techniques such as microarrays and high-throughput sequencing has revolutionized our ability to examine messenger RNA (mRNA) expression within the respiratory system. Importantly, these approaches have also uncovered the widespread expression of “noncoding RNAs,” including microRNAs and long noncoding RNAs, which impact biologic responses through the regulation of mRNA transcription and/or translation. To date, most studies of the role of noncoding RNAs have focused on microRNAs, which regulate mRNA translation via the RNA interference pathway. These studies have shown changes in microRNA expression in cells and tissues derived from patients with asthma, pulmonary fibrosis, cystic fibrosis, COPD, and non-small cell lung cancer. Although the evidence is currently limited, we review the work that has been carried out in cell and animal models that has identified the function and mechanism of action of a small number of these microRNAs in disease etiology. In addition to microRNAs, we assess the emerging evidence that long noncoding RNAs regulate respiratory phenotype. Because these investigations into long noncoding RNAs were performed almost exclusively in non-small cell lung cancer, future work will need to extend these into other respiratory diseases and to analyze how microRNAs and long noncoding RNAs interact to regulate mRNA expression. From a clinical perspective, the targeting of noncoding RNAs as a novel therapeutic approach will require a deeper understanding of their function and mechanism of action. However, in the short term, changes in miRNA and long noncoding RNA expression are likely to be of use as biomarkers for disease stratification and/or assessment of drug action.