The Novel Regulatory Role of the lncRNA-miRNA-mRNA Axis in Chronic Inflammatory Airway Diseases

Abstract

Chronic inflammatory airway diseases, characterized by airway inflammation and airway remodelling, are increasing as a cause of morbidity and mortality for all age groups and races across the world. The underlying molecular mechanisms involved in chronic inflammatory airway diseases have not been fully explored. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have recently attracted much attention for their roles in the regulation of a variety of biological processes. A number of studies have confirmed that both lncRNAs and miRNAs can regulate the initiation and progression of chronic airway diseases by targeting mRNAs and regulating different cellular processes, such as proliferation, apoptosis, inflammation, migration, and epithelial-mesenchymal transition (EMT). Recently, accumulative evidence has shown that the novel regulatory mechanism underlying the interaction among lncRNAs, miRNAs and messenger RNAs (mRNAs) plays a critical role in the pathophysiological processes of chronic inflammatory airway diseases. In this review, we comprehensively summarized the regulatory roles of the lncRNA-miRNA-mRNA network in different cell types and their potential roles as biomarkers, indicators of comorbidities or therapeutic targets for chronic inflammatory airway diseases, particularly chronic obstructive pulmonary disease (COPD) and asthma.

Keywords: COPD; asthma; long noncoding RNAs; mRNAs; miRNAs.

FIGURE 1

LncRNAs can act as a sponge for microRNAs. By binding to these microRNAs, they prevent microRNAs from binding to their target mRNAs, thereby abolishing post-transcriptional regulation.

FIGURE 2

The lncRNA-miRNA crosstalk is involved in the pathogenesis of COPD by regulating bronchial epithelial cells and pulmonary microvascular endothelial cells. Different lncRNAs regulate different miRNAs through the sponge effect, and then inhibit Mrna. The dotted boxes in the picture show typical lncRNA-miRNA interactions that function in COPD, which correspond to the cellular process they act on through pink arrows. HPMECs: Human pulmonary microvascular endothelial cells; EMT: epithelial–mesenchymal transition.

FIGURE 3

The lncRNA-miRNA crosstalk is involved in the pathogenesis of asthma by regulating CD4⁺ T cells and airway smooth muscle cells. Different lncRNAs regulate different miRNAs through the sponge effect, and then inhibit Mrna. The dotted boxes in the picture show typical lncRNA-miRNA interactions that function in asthma, which correspond to the cellular process they act on through pink arrows. DC: Dendritic cell; ASMCs: airway smooth muscle cells.