Prediction of Differentially Expressed miRNAs as Potential Biomarkers for Aniridia-Associated Keratopathy based on Expression Profile Analyses

Abstract Background: Aniridia is a rare hereditary disorder that affects most structures of the eyes. This autosomal dominant disorder is caused by haploinsufficiency of Pax6, a critical gene for proper development of the eye. This study attempted to identify novel diagnostic differentially expressed miRNAs and related mRNAs to develop a deeper understanding of the molecular mechanisms and to provide new ideas for the diagnosis and treatment of aniridia-associated keratopathy (AAK). Methods: The miRNA and mRNA expression data were downloaded from GEO for differential expression analysis. R programs, WGCNA, and miRNA targets were used to identify differentially expressed genes (DEGs). The R package was used to screen candidate miRNAs as potential biomarkers, and predicted targets and DEG intersections were determined. A regulatory network between optimal differentially expressed miRNA and DEGs was then constructed. Function analysis and pathway enrichment of miRNA and mRNA were both performed. In addition, transcription factors (TFs) of differential miRNAs and molecular compounds that may be efficient were predicted.Results: We used three methods to identify DEGs: 509 differential genes were screened by R, 1522 by WGCNA, and 732 by prediction of different miRNA targets. In total, 18 DEGs were found, encompassing 9 upregulated genes and 9 downregulated genes. Eight differentially expressed miRNAs were identified using the R package: five were upregulated and three were downregulated. Among them, three miRNAs (miR-204-5p, miR-224-5p, and miR-30a-5p) were considered optimal potential biomarkers, and their regulatory network with DEGs was created by Cytoscape. IL-4-mediated signaling events were the most enriched signaling pathways. Based on these DEGs, CHL1 and SOCS3 were most closely associated with clinical characteristics, which related to sex and stage separately.Conclusions: This study identified novel diagnostic differentially expressed miRNAs and related mRNAs by developing a deeper understanding of the molecular mechanisms, based on that we provided new ideas for the diagnosis and treatment of AAK.