Analysis of miRNA Profiles and the Regulatory Network in Congenital Pulmonary Airway Malformations

Abstract

Background: Specific diagnostic markers for congenital pulmonary airway malformations (CPAMs) have not yet been discovered. This study intends to detect differentially expressed miRNAs in type I and type II CPAMs by using a miRNA chip and clarify the feasibility of miRNAs as different CPAM typing markers.Methods: Lung tissues of type I and type II CPAMs were collected and used to assess the differentially expressed miRNAs using a miRNA chip after evaluation using hematoxylin–eosin staining and Masson staining. Quantitative reverse transcription-polymerase chain reaction and fluorescence in situ hybridization were used to verify the quality of the miRNA chip. The function and pathways of related differentially expressed miRNAs were analyzed by Gene Ontology Enrichment (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, respectively. Targets of miRNAs were predicted by targetscan7.1 and mirdbV6 and the network between miRNA and mRNA was established using Cystoscope software.Results: In total, 394/34 upregulated and 321/72 downregulated miRNAs were found in type I and type II CPAMs, respectively. GO and KEGG analysis showed that different pathways are involved in the regulation of CPAM, including platelet activation, Ras, MAPK, FoxO, and PI3K-Akt signaling pathways. miRNA–mRNA network analysis confirmed four major miRNAs in CPAM, including miR-4731-5p to complexin 2, miR-3150a-3p to vesicle amine transport 1, miR-32-5p to F-box and WD repeat domain containing 7, and miR-454-3p to SLAIN motif family member 1.Conclusion: In summary, we have identified four candidate miRNAs and pathways related to different pattern CPAMs, which provide a new perspective for CPAM research and treatment.

The Role of the miR-548au-3p/CA12 Axis in Tracheal Chondrogenesis in Congenital Pulmonary Airway Malformations

“…In this study, we set out to explore the role of miRNAs in the pathology of CPAM, a congenital disorder of the lung. Zeng et al [13] previously provided genomic insights into this 10…”

“…MicroRNAs (miRNAs), which are highly conserved short noncoding RNA molecules, play an essential role in the onset and progression of lung diseases [9,10] by regulating a variety of biological functions, including cell differentiation and proliferation and organ morphogenesis [11,12]. The expression and role of miRNAs in CPAM were recently reported in a recent study by Zeng et al [13], who identified differentially expressed miRNAs in CPAMs, using miRNA chip analysis, in patients with CPAM. Specifically, the authors reported upregulation of miR-4523 and miR-548au-3p and downregulation of miR-21-3p, miR-590-3p, and miR-146a-3p in patients with type I-II CPAM compared with adjacent lesion tissue.…”

Serum microRNAs targeting ACE2 and RAB14 genes distinguish asymptomatic from critical COVID-19 patients

“…32 Moreover, hsa-miR-32-5p and miR-98-3p, also targeting RAB14, were identified as crucial lung cancer-associated miRNAs, [33][34][35] and their deregulation levels were identified in several respiratory disorders, such as acute respiratory distress syndrome, 36,37 bronchopulmonary dysplasia, 38 and congenital pulmonary airway malformations. 39 Besides, these miR-NAs have been previously related with viral processes. For instance, miR-32-5p has a significant regulatory role in avian hepatitis A viral infection, 40 visna maedi virus, 41 and caprine arthritis encephalitis viruses, 41 while the deregulation of the expression miR-98 has been described in a mouse model of West Nile virus neuropathogenesis.…”