Comprehensive analysis of circRNA expression pattern and circRNA–mRNA–miRNA network in Ctenopharyngodon idellus kidney (CIK) cells after grass carp reovirus (GCRV) infection

Abstract

Grass carp reovirus (GCRV) causes grass carp hemorrhage disease and is one of the most damaging factors in the culture of grass carp (Ctenopharyngodon idellus). Until now, the mechanisms underlying GCRV infection have been largely unknown. To explore the molecular responses to GCRV infection in C. idellus kidney (CIK) cells, we used high-throughput sequencing to investigate the circRNA, mRNA, and miRNA expression patterns and the circRNA–miRNA–mRNA network. A total of 76 circRNAs, 798 mRNAs, and 186 miRNAs were identified as differentially expressed (DE) RNAs in GCRV-infected cells compared with uninfected cells, of which 40 circRNAs, 658 mRNAs, and 146 miRNAs were upregulated, and 36 circRNAs, 140 mRNAs, and 40 miRNAs were downregulated (fold change >2, p < .05). A Gene Ontology (GO) analysis of the DE circRNA parental genes, mRNAs, and miRNA target genes was performed. The parental genes of the DE circRNAs, the DE mRNAs, and the target genes of the DE miRNAs were mainly enriched in metal-ion-binding-, immune-, and DNA-replication-related items, respectively. A KEGG pathway analysis showed that the DE circRNA parental genes, DE mRNAs, and miRNA target genes were predominantly enriched in endocytosis-, immune-, and infection-related pathways, respectively. The miRNA–target interactions were also predicted and competing regulatory networks of endogenous RNAs were constructed based on the DE RNAs. Our prediction results suggest that the circRNA-2780/cik–miRNA-7796/KAT6B, circRNA-1351/cik-miRNA–10648/B2L14 and circRNA-1591/cik-miR-8141/AMPD3 axes may be associated with GCRV infection. This study suggests that the crosstalk between circRNAs and their competing mRNAs play crucial roles in GCRV infection.