Institute of Inflammation and Repair, The University of Manchester, Manchester, England; Manchester Academic Health Sciences Centre and North West Lung Centre, University Hospital of South Manchester, Manchester, England.
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, England.
Chest. 2014 Jul;146(1):193-204. doi: 10.1378/chest.13-2736.
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.
微阵列和高通量测序等技术的出现极大地改变了我们检查呼吸系统中信使 RNA（mRNA）表达的能力。重要的是，这些方法还揭示了“非编码 RNA”的广泛表达，包括 microRNAs 和长非编码 RNA，它们通过调节 mRNA 转录和/或翻译来影响生物反应。迄今为止，非编码 RNA 作用的大多数研究都集中在 microRNAs 上，microRNAs 通过 RNA 干扰途径调节 mRNA 翻译。这些研究表明，哮喘、肺纤维化、囊性纤维化、COPD 和非小细胞肺癌患者的细胞和组织中 microRNA 表达发生了变化。尽管目前证据有限，但我们回顾了在细胞和动物模型中开展的工作，这些工作确定了少数这些 microRNAs 在疾病发病机制中的功能和作用机制。除了 microRNAs 之外，我们还评估了长非编码 RNA 调节呼吸表型的新出现证据。由于这些关于长非编码 RNA 的研究几乎仅在非小细胞肺癌中进行，因此未来的工作将需要将这些研究扩展到其他呼吸系统疾病，并分析 microRNAs 和长非编码 RNA 如何相互作用以调节 mRNA 表达。从临床角度来看，将非编码 RNA 作为一种新的治疗方法需要更深入地了解它们的功能和作用机制。然而，短期内，miRNA 和长非编码 RNA 表达的变化可能作为疾病分层和/或药物作用评估的生物标志物具有一定的作用。
