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Bronchial epithelial cells contribute to asthmatic pathogenesis. Within this study, hsa-miR-30d-3p and hsa-miR-30a-3p have been identified in the final leading ten ceRNAs. Preceding bioinformatic analyses showed that hsamiR-30d-3p was connected with non-small cell lung cancer and inhibited Cereblon custom synthesis epidermal growth issue receptor-targeted medicineFrontiers in Molecular Biosciences | www.frontiersin.orgJuly 2021 | Volume 8 | ArticleChen et al.A ceRNA Network in AsthmaFIGURE 6 | Protein-protein interaction network of your 19 hub-genes target network. Protein-protein interaction network in the 19 hub-genes target network was constructed working with GeneMANIA database. The colors on the edges within the network indicated different GSK-3 web bioinformatics approaches made use of, which includes co-expression, website prediction, shared protein domains, and co-localization. The colors of the nodes within the network indicated the functional enrichment evaluation in the query gene list.therapy (Wang et al., 2017; Pan et al., 2019). Hsa-miR-30d-3p has also been implicated as a novel biomarker for treatment monitoring of postmenopausal osteoporosis (Weigl et al., 2021) and cerebral ischemia-reperfusion injury (Jin et al., 2021). However, hsa-miR30d-3p has not been reported in asthma however. Hsa-miR-30a-3p was reported to regulate the tumorigenesis in several cancer, which include gastric cancer (Wang et al., 2019b), lung adenocarcinoma (Wang et al., 2020), and pancreatic ductal adenocarcinoma (Shimomura et al., 2020). Li and other people reported that hsa-miR-30a-3p regulates eosinophil activity through targeting CCR3 in asthma (Li et al., 2020). Hsa_circ_0001585, hsa_circ_0078031, and hsa_circ_0000552 were the 3 circRNAs ultimately identified in the ceRNA network. So far, there were no reports on these circRNAs. As shown inSupplementary Table 1, these circRNAs have been mostly intergenic circRNAs with fairly lengthy spliced lengths, bringing obstacles for study. Having said that, the exceeding spliced length of these circRNAs could provide numerous miRNA response elements for miRNA to bind. In summary, we integrated six microarray datasets (5 mRNA datasets and one particular miRNA dataset) and utilized the RRA approach to get robust DEGs and robust hub genes. Depending on the prediction of three miRNA-related databases (Targetscan, miRDB, and miRWalk) and one circRNArelated database (ENCORI), an epithelial circRNAmiRNA-mRNA network was finally constructed and the best ten epithelial ceRNAs had been identified. This epithelialFrontiers in Molecular Biosciences | www.frontiersin.orgJuly 2021 | Volume 8 | ArticleChen et al.A ceRNA Network in AsthmaFIGURE 7 | CircRNA-miRNA-mRNA network building. (A) The volcano plot of differentially expressed miRNAs of GSE142237. The upregulated miRNAs were marked in red, although the downregulated miRNAs have been marked in blue. The gray dots represented miRNAs with no significant difference. (B) The Venn diagram showed the intersection in between the miRNAs targeting upregulated hub genes inside the prediction result (red) along with the downregulated miRNAs of GSE142237 (blue). (C) The Venn diagram showed the intersection amongst the miRNAs targeting downregulated hub genes in the prediction result (blue) along with the upregulated miRNAs of GSE142237 (red). (D) The circRNAmiRNA-mRNA network. CircRNAs were marked as octagons, miRNAs had been marked as ellipses, and mRNAs were marked as diamonds. The size on the nodes indicated the degree of your connection. Up-regulated molecules had been marked in red, though down-regulated molecules were marked in.

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