Aberrant MicroRNAomics in Pulmonary Complications: Implications in Lung Health and Diseases

Abstract

Over the last few decades, evolutionarily conserved molecular networks have emerged as important regulators in the expression and function of eukaryotic genomes. Recently, miRNAs (miRNAs), a large family of small, non-coding regulatory RNAs were identified in these networks as regulators of endogenous genes by exerting post-transcriptional gene regulation activity in a broad range of eukaryotic species. Dysregulation of miRNA expression correlates with aberrant gene expression and can play an essential role in human health and disease. In the context of the lung, miRNAs have been implicated in organogenesis programming, such as proliferation, differentiation, and morphogenesis. Gain- or loss-of-function studies revealed their pivotal roles as regulators of disease development, potential therapeutic candidates/targets, and clinical biomarkers. An altered microRNAome has been attributed to several pulmonary diseases, such as asthma, chronic pulmonary obstructive disease, cystic fibrosis, lung cancer, and idiopathic pulmonary fibrosis. Considering the relevant roles and functions of miRNAs under physiological and pathological conditions, they may lead to the invention of new diagnostic and therapeutic tools. This review will focus on recent advances in understanding the role of miRNAs in lung development, lung health, and diseases, while also exploring the progress and prospects of their application as therapeutic leads or as biomarkers.

Alpha-1 Antitrypsin—A Target for MicroRNA-Based Therapeutic Development for Cystic Fibrosis

“…miR-221 is increased in CF bronchial brushings, whilst its target, activating transcription factor 6 (ATF6; a transcription factor involved in the UPR), is decreased [138]. The role of dysregulated miRNAs in CF and other lung diseases has been more extensively reviewed elsewhere, for example Glasgow et al [139] and Dutta et al [140].…”

MiR-1307-5p targeting TRAF3 upregulates the MAPK/NF-κB pathway and promotes lung adenocarcinoma proliferation

“…MiRNAs are small non-coding regulatory RNAs that bind to the 3′ untranslated region (3′ UTR) of mRNA and regulate its function and that of endogenous genes by influencing the translation process [22,23]. Dysregulation of miRNA expression is associated with abnormal gene expression and is involved in the development of lung adenocarcinoma, such as cell proliferation, apoptosis, migration, invasion, and differentiation [24,25].…”

Role of Non-Coding RNAs in Lung Circadian Clock Related Diseases

“…MicroRNAs (miRNAs) are a class of short (20-23-nucleotide), endogenous, single-stranded non-coding RNAs that play important roles in regulating the expression of target genes by directly binding to their mRNAs [54,55]. miRNA biogenesis is a sequential action of both nuclear and cytoplasmic processes.…”

“…The miR-142-5p and miR-142-3p miRNAs play an important role in negative feedback regulation of molecular clock, with miR-142-3p and miR-142-5p suppressing BMAL1 and SIRT1, respectively [67][68][69]. MiR-142 expression demonstrates circadian rhythmicity and is CLOCK-controlled, with CLOCK:BMAL1 binding to upstream E-box elements of miR-142 [55,69]. Hence miR-142 serves as a core clock-controlled miRNA.…”