Role of the XIST-miR-181a-COL4A1 axis in the development and progression of keratoconus.

ABSTRACT

Background: As a disorder occurs in the eyes, keratoconus (KC) is induced by the thinning of the corneal stroma. This study was designed to reveal the key long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs involved in the mechanisms of KC. Methods: Transcriptome RNA-seq data set GSE112155 was acquired from the Gene Expression Omnibus database, which contained 10 KC samples and 10 myopic control samples. Using the edgeR package, the differentially expressed (DE)-mRNAs between KC and control samples were screened. The DE-lncRNAs and DE-miRNAs in this data set were identified using the HUGO Gene Nomenclature Committee (HGNC). Using the pheatmap package, bidirectional hierarchical clustering of the DE-RNAs was conducted. Then, an enrichment analysis of the DE-mRNAs was performed using the DAVID tool. Moreover, a competitive endogenous RNA (ceRNA) regulatory network was built using the Cytoscape software. After KC-associated pathways were searched within the Comparative Toxicogenomics Database, a KC-associated ceRNA regulatory network was constructed. Results: There were 282 DE-lncRNAs (192 upregulated and 90 downregulated), 40 DE-miRNAs (29 upregulated and 11 downregulated), and 910 DE-mRNAs (554 upregulated and 356 downregulated) between the KC and control samples. A total of 34 functional terms and 9 pathways were enriched for the DE-mRNAs. In addition, 6 mRNAs (including PPARG, HLA-B, COL4A1, and COL4A2), 5 miRNAs (including miR-181a), 9 lncRNAs (including XIST), and the XIST-miR-181a-COL4A1 axis were involved in the KC-associated ceRNA regulatory network. Conclusions: PPARG, HLA-B, COL4A1, COL4A2, miR-181a, and XIST might be correlated with the development of KC. Further, the XIST-miR-181a-COL4A1 axis might be implicated in the pathogenesis of KC.