The Roles of MicroRNAs and Protein Components of the MicroRNA Pathway in Lung Development and Diseases

Abstract

Decades of studies have shown evolutionarily conserved molecular networks consisting of transcriptional factors, diffusing growth factors, and signaling pathways that regulate proper lung development. Recently, microRNAs (miRNAs), small, noncoding regulatory RNAs, have been integrated into these networks. Significant advances have been made in characterizing the developmental stage-or cell type-specific miRNAs during lung development by using approaches such as genome-wide profiling and in situ hybridization. Results from gain-or loss-of-function studies revealed pivotal roles of protein components of the miRNA pathway and individual miRNAs in regulating proliferation, apoptosis, differentiation, and morphogenesis during lung development. Aberrant expression or functions of these components have been associated with pulmonary disorders, suggesting their involvement in pathogenesis of these diseases. Moreover, genetically modified mice generated in these studies have become useful models of human lung diseases. Challenges in this field include characterization of collective function and responsible targets of miRNAs specifically expressed during lung development, and translation of these basic findings into clinically relevant information for better understanding of human diseases. The goal of this review is to discuss the recent progress on the understanding of how the miRNA pathway regulates lung development, how dysregulation of miRNA activities contributes to pathogenesis of related pulmonary diseases, and to identify relevant questions and future directions.

Asthma diagnosis using integrated analysis of eosinophil microRNAs

“…Among the discovered miRNAs, some have been found for the first time in this study (ie, miR‐1246 and miR‐1290), while others have already been described and associated with asthmatic pathology . For example, miR‐21 is overexpressed in the asthmatic airways and miR‐146b‐5p is highly expressed in stimulated asthmatic airway smooth muscle cells …”

MicroRNA-661 promotes non-small cell lung cancer progression by directly targeting RUNX3

“…Lung cancer is the most common malignancy in humans and is the primary cause of cancer-related mortality in both men and women globally (1,2). Previous studies demonstrated that accumulation of permanent genetic alterations in combination with dynamic epigenetic alterations results in lung cancer formation and progression (3,4). Lung cancer can be divided into two major groups based on pathological features: Small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) (5).…”

The effects of tracheal occlusion on Wnt signaling in a rabbit model of congenital diaphragmatic hernia

“…Recently it has become apparent that a complex interplay occurs between miRNAs and mRNAs. miRNAs are non-coding RNAs that function as post-transcriptional regulators of gene expression [56]. miR-33 is an upstream regulator of the Wnt signaling pathway and was found to be downregulated in CDH rat fetuses [50].…”

“…miR-124 regulates lung epithelial maturation and has been linked to the Wnt/ catenin signaling pathway [53]. miR-142, which is highly expressed in mesenchyme during early lung development, has also been found to interact with the Wnt/ catenin signaling pathway [54][55][56]. The overexpression of miR-375 was found to inhibit alveolar epithelial differentiation by targeting the Wnt/ catenin signaling pathway [57,58].…”