Circular RNA Transcriptomic Analysis of Primary Human Brain Microvascular Endothelial Cells Infected with Meningitic Escherichia coli

Abstract

With their essential regulatory roles in gene expression and high abundance in the brain, circular RNAs (circRNAs) have recently attracted considerable attention. Many studies have shown that circRNAs play important roles in the pathology of CNS diseases, but whether circRNAs participate in E. coli-induced bacterial meningitis is unclear. We used high-throughput sequencing to analyze the transcriptional profiles of host circRNAs in primary brain microvascular endothelial cells in response to meningitic E. coli. A total of 308 circRNAs were significantly altered, including 140 upregulated and 168 downregulated ones (p < 0.05). Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology enrichment of the parental genes of these altered circRNAs indicated that they are likely to be involved in diverse biological processes via influencing the expression of their parental genes. Coupled with our previous mRNA and microRNA sequencing data, a competing endogenous RNA analysis was performed, and the potential regulatory network was preliminarily constructed and validated. By revealing the transcriptional profiles of the host circRNAs involved in E. coli meningitis, it is envisaged that the novel insight gained into the regulatory mechanisms of circRNAs in the development of bacterial meningitis will lead to better understanding of how to prevent and treat bacterial CNS infections. Keywords: circular RNAs, CNS, brain microvascular endothelial cells, meningitic Escherichia coli, competing endogenous RNAs