miRNAs in Lung Development and Diseases

Abstract

The development of the lung involves a diverse group of molecules that regulate cellular processes, organ formation, and maturation. The various stages of lung development are marked by accumulation of small RNAs that promote or repress underlying mechanisms, depending on the physiological environment in utero and postnatally. To some extent, the pathogenesis of various lung diseases is regulated by small RNAs. In this review, we discussed miRNAs regulation of lung development and diseases, that is, COPD, asthma, pulmonary fibrosis, and pulmonary arterial hypertension, and also highlighted possible connotations for human lung health.After fertilization in the mouse, total miRNA in the two-cell-stage embryo was demonstrated to be significantly lower than the levels in one-cell zygote [15]. Notably, total miRNA in the four-cell-stage embryo was higher than the levels in the two-cell-stage embryo [15]. In the early mouse embryo, miR-127 was upregulated at E6.5 and E7.5 [16]. Overexpression of miR-127 in mouse embryonic stem cells, which differentiated into embryoid bodies, increased the mRNA levels of Gsc, Foxa2, and Brachyury (mesendoderm markers), but elicited no change in Pax6 and Otx2 (ectoderm markers) three days after transfection. Inhibition of miR-127 showed opposite regulation of Gsc, Foxa2, and Brachyury. miR-127, moreover, was suggested to control mesendoderm differentiation [16]. miR-326 regulated sonic hedgehog signaling by targeting Smo and Gli2 [17]. The inhibition of smoothened in cultured explanted E12 mouse lung resulted in the expansion of distal epithelium, and disruption of normal branching pattern and mesenchymal integrity [17]. Another study described the functional role of miR-142-3p in the mouse embryonic lung mesenchyme. The miRNA was shown to regulate adenomatous polyposis coli to further modulate Wnt signaling [18]. Taken together, miR-142-3p regulated the proliferation and differentiation of mesenchymal progenitors in the mouse embryonic lung [18].In the developing mouse lung, the level of miR-17 was stable (E11.5-E16.5), predominantly at the pseudoglandular stage, with higher epithelial levels at E12.5 [19]. Simultaneous knockdown of miR-17 and its paralogs, miR-20a and miR-106b, for 72 h in epithelial lung explants altered branching, even in FGF10-treated condition [19]. In the human fetal lung, miR-449a was upregulated at 18-20 weeks (canalicular stage), and in the mouse embryonic lung, miR-449a level was increased from E15.5 to E18.5 [20]. The inhibition of miR-449a in E16.5 mouse lung culture (end of pseudoglandular stage) increased the mRNA levels of Mycn and Sox9, and the protein levels of Ki-67 and SOX9 particularly in the distal epithelial region [20].Knockout of miR-26a-1/miR-26a-2 in the mouse promoted the formation of dilated lumens and aerated regions at the beginning of the canalicular stage (E16.5) of lung development [21]. Results at the saccular stage (E18.5) also indicated large lamellar bodies, and increased SP-A, SP-B, and SP-C protein levels in miR-26a knockout mice....

Circ-BPTF Associated Pulmonary Vascular Remodeling in COPD Via Promoting Smooth Muscle Cells Proliferation by MiR-486-5p/CEMIP Axis

“…MiRNAs are small noncoding RNAs involved in the regulation of posttranscriptional gene expression (Negi et al 2017). miRNA dysregulations have been reported as promoter of the development of various diseases including cancers (Boateng et al 2020). Indeed, impairment of miRNA expression has been involved in vascular cell remodeling processes such as adventitial broblast migration, PASMC proliferation and pulmonary arterial endothelial cell dysfunction observed (Zhou et al 2015).…”

Developmental Pathways Underlying Lung Development and Congenital Lung Disorders

“…More recently, epigenetic alterations, particularly microRNAs, have been associated with CDH pathophysiology. Several miRNAs have been associated with different lung developmental stages [ 204 ]. In the CDH context, miR-200b is upregulated in both human and animal samples.…”

A Timely Review of Cross-Kingdom Regulation of Plant-Derived MicroRNAs

“…By binding at nucleotide sequence CCAAGCG, located on the open reading frame of low-density lipoprotein receptor adapter protein 1 (LDLRAP1), MIR168a inhibits LDLRAP1 expression, and thereby decreases LDL removal from mouse plasma. This pioneering work indicating that ingestion of plants containing high-content of functional miRNAs might be a promising way for clinical applications, because deregulation of miRNAs is involved in the pathogenesis of many human diseases such as cancers, immunodeficiency, cardiovascular diseases, and, with the new data emerging, lung diseases ( Boateng and Krauss-Etschmann, 2020 ). More importantly, rapidly accumulating data have implicated both endogenous and dietary exogenous miRNAs regulate gene expression mainly at the post-transcriptional level via direct cleavage of transcripts ( Sanchita et al, 2018 ; Ren et al, 2019 ).…”