Construction of ceRNA network and identification of hub genes in aniridia-associated keratopathy using bioinformatics analysis

Jiawen Wu; Daowei Zhang; Jihong Wu; Shenghai Zhang

doi:10.3389/fgene.2022.997581

Construction of ceRNA network and identification of hub genes in aniridia-associated keratopathy using bioinformatics analysis

Front Genet. 2022 Sep 23:13:997581. doi: 10.3389/fgene.2022.997581. eCollection 2022.

Authors

Jiawen Wu¹, Daowei Zhang¹, Jihong Wu^{1

2

3

4}, Shenghai Zhang^{1

2

3

4}

Affiliations

¹ Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, China.
² Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China.
³ State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Shanghai, China.
⁴ Key Laboratory of Myopia, Ministry of Health, Shanghai, China.

Abstract

Aniridia-associated keratopathy (AAK) is characteristic at ocular surface of aniridia caused by haploinsufficiency of PAX6. Competing endogenous RNA (ceRNA) has been reported to play an important role in various diseases, whereas its function on AAK is unclear. The microarray data of 20 AAK patients and 20 healthy people were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed lncRNAs, miRNAs, and mRNAs were analyzed using "limma" packages and weighted gene co-expression network analysis (WGCNA). A ceRNA network was constructed by Cytoscape 3.9.1, and miR-224-5p, miR-30a-5p, and miR-204-5p were at the center of the network. CIBERSORTx algorithm and ssGSEA analyses revealed that AAK was associated with immune cell infiltration, showing that activated Mast cells increased while resting Mast cells decreased and NK cells decreased in AAK. Type II INF Response, CCR, parainflammation, T cell co-stimulation, and APC co-stimulation of AAK patients differed from healthy individuals. Additionally, the ROC curve of five genes, MITF(AUC = 0.988), RHOB(AUC = 0.973), JUN(AUC = 0.953), PLAUR (AUC = 0.925), and ARG2 (AUC = 0.915) with high confidence in predicting AAK were identified. Gene set enrichment analysis (GSEA) analysis of hub genes enriched in the IL-17 signaling pathway.

Keywords: AAK; IL-17 signaling pathway; WGCNA; biomarkers; ceRNA network; immune microenvironment; ocular surface.