Identification of a circRNA/miRNA/mRNA ceRNA Network as a Cell Cycle-Related Regulator for Chronic Sinusitis with Nasal Polyps

Abstract

Purpose To explore the mechanisms by which circRNA/miRNA/mRNA competitive endogenous RNAs (ceRNA) networks regulate CRSwNP. Methods The expression profiles of circRNAs, miRNAs, and mRNAs from patients with CRSwNP and control subjects were acquired from the Gene Expression Omnibus database. The circRNA/miRNA/mRNA ceRNA network was constructed based on the predicted circRNA–miRNA interactions and miRNA–mRNA interactions. Hub-mRNAs were screened by protein–protein interaction network analysis and Cytoscape molecular complex detection. The expression of factors in tissue and in hsa_circ_0031594 siRNA transfection cells was verified by RT-qPCR and the association between them was revealed by Spearman correlation analysis. Receiver operating characteristic curve analysis was performed with the pROC R package. Results The differential expression of 5423 circRNAs, 415 miRNAs, and 3673 mRNAs was identified in CRSwNP subjects compared to control subjects. Among these, 9 circRNAs, 39 miRNAs, and 78 mRNAs were screened to construct a ceRNA network. Ultimately, a subnetwork including circRNA hsa_circ_0031594, hsa-miR-1260b, hsa-miR-6507-5p, NCAPG2, RACGAP1, CHEK1 and PRC1 was screened out. RT-qPCR validated that the expression of hsa_circ_0031594, NCAPG2, PRC1 was significantly increased, and hsa-miR-1260b and hsa-miR-6507-5p were expressed significantly less in patients with CRSwNP than in control subjects. In addition, the AUCs of hsa_circ_0031594, hsa-miR-1260b, hsa-miR-6507-5p, NCAPG2, and PRC1 to discriminate CRSwNP patients were 0.995, 0.842, 0.862, 0.765, and 0.816. Spearman correlation showed that the expression of hsa_circ_0031594 was negatively correlated with hsa-miR-1260b and hsa-miR-6507-5p, and positively correlated with NCAPG2 and PRC1. In human nasal epithelial cell (HNEpC) line, knocking down hsa_circ_0031594 could increase the expression of hsa-miR-1260b and hsa-miR-6507-5p, and reduce the expression of NCAPG2 and PRC1. Conclusion CeRNA networks including hsa_circ_0031594, hsa-miR-1260b, and NCAPG2, and hsa_circ_0031594, hsa-miR-6507-5p, and PRC1 may be key regulators for CRSwNP occurrence, and may be potential targets for the pathogenesis and treatment development of CRSwNP.

Insights into the epigenetics of chronic rhinosinusitis with and without nasal polyps: a systematic review

“…One study was exclusively done in a murine model of CRS ( 56 ), whereas five studies looked at murine models in addition to human subjects ( 42 , 57 – 60 ). Overall, differences in miRNA and lncRNA profiles were found between CRSwNP and controls ( 40 – 44 , 46 , 47 , 49 , 61 , 62 , 63 – 66 ). The specific miRNAs that were investigated found some of the target genes and pathways as follows: IL-10 ( 67 , 68 ), IL-5 ( 64 ), IL-6 ( 69 ), aryl hydrocarbon receptor (AHR) (transcription factor that also modulates immune response) ( 53 ), EGR2 ( 51 ), TGF beta-1 ( 52 , 62 , 70 – 73 ) and tumor necrosis factor (TNF) alpha ( 54 , 60 ), glucagon-like peptide-1 and IL-33 ( 55 ), EGF ( 74 ), IRF4 ( 42 ), PI3K/AKT pathway ( 40 , 56 , 58 , 65 , 75 ), mucin secretion ( 76 ), MMP ( 77 ), EMT, VE-cadherin ( 78 ), and ROR alpha ( 61 ).…”

“…Out of the 44 studies investigating the role of non-coding RNAs, most studies investigated miRNAs, and only a few investigated other RNA types such as lncRNAs ( 40 – 44 ), siRNAs ( 45 ), and circRNAs ( 46 , 47 ). Six studies used pre-existing GEO data sets to identify transcriptome-wide miRNA or lncRNA profiles of CRSwNP vs. controls, either exclusively or in conjunction with in vivo studies on CRS subjects ( 40 – 42 , 44 , 46 , 48 ). Most studies had control subjects.…”

Cirscan: a shiny application to identify differentially active sponge mechanisms and visualize circRNA-miRNA-mRNA networks

“…miRNA and mRNA expression data), and to their predictions databases restricted to interactions between miRNA and mRNA [11, 12]. Moreover, the studies focusing on circRNA-miRNA-mRNA networks have not developed a computational tool that automates the search for large-scale ce-circRNA [13, 14, 15, 16, 17, 18, 19]. Two circRNA functional annotation databases predicting sponge mechanisms involving circRNAs in several tissues have been developed, but they do not allow users to query their own transcriptomic datasets on a large scale, they most often limite queries to circRNA identifiers or sequences [20, 21].…”

Hsa_circ_0099630 knockdown induces the proliferation and osteogenic differentiation and attenuates the apoptosis of porphyromonas gingivalis lipopolysaccharide–induced human periodontal ligament fibroblasts

“…Based on the circbase database, we discovered that hsa_circ_0099630 is located in chr12:97885421-97924637, its best transcript is NR_024037, and its gene symbol is rhabdomyosarcoma 2 associated transcript (RMST). Additionally, a recent microarray screening study showed that hsa_circ_0099630 was upregulated in chronic sinusitis with nasal polyps ( 16 ). Thus, we speculated that hsa_circ_0099630 may be relevant to inflammation and may play a crucial role in periodontitis.…”