Novel insights into miRNA in lung and heart inflammatory diseases

Abstract

MicroRNAs (miRNAs) are noncoding regulatory sequences that govern posttranscriptional inhibition of genes through binding mainly at regulatory regions. The regulatory mechanism of miRNAs are influenced by complex crosstalk among single nucleotide polymorphisms (SNPs) within miRNA seed region and epigenetic modifications. Circulating miRNAs exhibit potential characteristics as stable biomarker. Functionally, miRNAs are involved in basic regulatory mechanisms of cells including inflammation. Thus, miRNA dysregulation, resulting in aberrant expression of a gene, is suggested to play an important role in disease susceptibility. This review focuses on the role of miRNA as diagnostic marker in pathogenesis of lung inflammatory diseases and in cardiac remodelling events during inflammation. From recent reports, In this context, the information about the models in which miRNAs expression were investigated including types of biological samples, as well as on the methods for miRNA validation and prediction/definition of their gene targets are emphasized in the review. Besides disease pathogenesis, promising role of miRNAs in early disease diagnosis and prognostication is also discussed. However, some miRNAs are also indicated with protective role. Thus, identifications and usage of such potential miRNAs as well as disruption of disease susceptible miRNAs using antagonists, antagomirs, are imperative and may provide a novel therapeutic approach towards combating the disease progression.

Figure 1

Biogenesis and role of micro-RNA (miRNA). The processing (★) step includes conversion of pri-miRNA to pre-miRNA through Drosha and DGCR8 and pre-miRNA to mature miRNA in the presence of dicer, PACT, and TRBP. In the mature miRNA, either of its strands is involved in RISC formation along with Ago-2. The complex is involved in transcriptional regulation (▲) by binding to site for transcription factors in the 5′-UTR, while it functions (▼) for mRNA degradation (by perfect pairing of its seed region) or transcriptional repression (by imperfect binding) of the target mRNA region. The mature circulatory miRNAs are also transported with microparticles such as membrane derived vesicles (exosomes and microvesicles), lipoproteins (HDL), or RNA binding proteins (RBPs) and remains protected from enzymatic degradation.

Figure 2

Role of miRNAs in mechanism of fibrosis. The downregulation of miR-200 and -192 (inhibits epithelial-mesenchymal transition, EMT) and miR-29 (prevents the deposition of extracellular matrix, ECM) promotes fibrosis. Further, miR-21 amplifies TGF-β signaling and promotes myofibroblasts phenotype in fibrosis. This is characterized by increased cellular factors* and expression of alpha-smooth muscle actin (α-SMA) and EDA-fibronectin.