Traumatic brain injury (TBI) causes high rates of worldwide death and morbidity because of the complex secondary injury cascade. Circular ribonucleic acid (RNA) (circRNA), a type of RNA that forms a covalently closed continuous loop, may be involved in the regulation of secondary injury because it is expressed widely in the brain and contributes to a large class of post-transcriptional regulators. Deep RNA sequencing (RNA-seq) and bioinformatic analysis were performed to investigate the expression profile and function of circRNAs in the mouse cortex after controlled cortical impact (CCI). A total of 19,794 circRNAs were identified, and 1315 were annotated in circBase. There were 191 filtered differentially expressed circRNAs (98 for up-regulated and 93 for down-regulated). The gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that inflammation, cell death, and repair of damage were the main biological processes and molecular mechanisms related to altered circRNAs. The pathway-circRNA interaction network revealed three core circRNAs and five corepathways related to TBI. The circRNA-messenger RNA (mRNA) interaction network and competitive endogenous RNA (ceRNA) analysis suggested potential microRNA (miRNA) sponges and target mRNAs. In addition to five optimal circRNA-miRNA-mRNA pairs were analyzed, circRNA_16895-miRNA myosin-10 (Myo 10) was predicted to regulate fragment crystallizable gamma receptors (FcγR)-mediated phagocytosis pathway. Four circRNAs were selected for quantitative real-time polymerase chain reaction analysis to validate the sequencing data. Our results provide promising functions of circRNAs aberrantly expressed in TBI to explore molecular mechanisms and potential therapeutic targets for its therapy.
Keywords: RNA-seq; bioinformatic analysis; ceRNA; circular RNAs (circRNAs); traumatic brain injury (TBI).