Construction and functional enrichment analysis of the competitive endogenous RNA regulatory network for nonarteritic anterior ischemic optic neuropathy based on high-throughput sequencing

Abstract

Based on the transcriptome high-throughput sequencing of nonarteritic anterior ischemic optic neuropathy (NAION), this study constructed a competitive endogenous RNA (ceRNA) network, enriched and analyzed it, screened long noncoding (lnc)RNAs and circular (circ)RNAs that may participate in the competitive endogenous mechanism in NAION, and inferred its function. Four milliliters of peripheral blood from NAION patients and the control group was extracted from clinical samples, transcriptome high-throughput sequencing was performed, and the sequencing data were visualized. Based on the principle of the ceRNA network, the lncRNA-micro (mi)RNA-messenger (m)RNA interaction axis and circRNA-miRNA‒mRNA interaction axes were constructed. The differentially expressed genes (DEGs) in the interaction axis were enriched and analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the functions and signalling pathways of lncRNAs and circRNAs in the interaction network were speculated. Fifty-one circRNAs were differentially expressed in the sequencing data: 25 were upregulated, and 26 were downregulated. For 996 differentially expressed lncRNAs, 317 were upregulated and 679 were downregulated, and for 1161 differentially expressed mRNAs, 698 were upregulated and 463 were downregulated. Thirty-three differentially expressed miRNAs, upregulated miRNA 18 and downregulated miRNA 15 were identified. After screening, 13 coexpressed mRNAs, 15 lncRNAs, and 3 miRNAs were finally constructed in the lncRNA-miRNA-mRNA network, and the circRNA-miRNA-mRNA network was constructed by 159 mRNAs, 26 miRNAs, and 34 circRNAs. In the lncRNA network, GO enrichment analysis obtained 182 biological processes, 12 cell components and 38 molecular functions, which are related mainly to the regulation of the activity of proteins and enzymes such as cyclic nucleotide-dependent protein kinase activity and magnesium ion-dependent protein serine/threonine phosphatase activity. KEGG analysis involved mainly the forkhead box O (FoxO) signalling pathway, apelin signalling pathway, etc. In the circRNA enrichment results, 353 biological processes, 52 cell components, and 45 molecular functions were obtained, involving mainly calcium channel regulation, neutrophil activation, mRNA transport, and metabolism. KEGG mainly involved the Wnt signalling pathway, apelin signalling pathway, Hippo signalling pathway, oxytocin signalling pathway, etc. This paper provides a new idea for lncRNAs and circRNAs to mediate the occurrence and development of NAION through the ceRNA mechanism. This study lays a foundation for the in-depth study of the pathogenesis of NAION.

Keywords: Enrichment analysis; High-throughput sequencing; Nonarteritic anterior ischemic optic neuropathy; ceRNA; circRNA; lncRNA.