Comprehensive circRNA-microRNA-mRNA network analysis revealed the novel regulatory mechanism of Trichosporon asahii infection

Background:Invasive Trichosporon asahii(T.asahii)infection frequently occurs with a high mortality in immunodeficient hosts,but the pathogenesis of T.asahii infection remains elusive.Circular RNAs(circRNAs)are a type of endogenous noncoding RNA that participate in various disease processes.However,the mechanism of circRNAs in T.asahii infection remains completely unknown.Methods:RNA sequencing(RNA-seq)was performed to analyze the expression profiles of circRNAs,microRNAs(miRNAs),and mRNAs in THP-1 cells infected with T.asahii or uninfected samples.Some of the RNA-seq results were verified by RT-qPCR.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were used to analyze the differentially expressed mRNAs.A circRNA-miRNA-mRNA network was constructed and verified by dual-luciferase reporter assay and overexpression experiments.Results:A total of 46 circRNAs,412 mRNAs and 47 miRNAs were differentially expressed at 12 h after T.asahii infection.GO and KEGG analyses showed that the differentially expressed mRNAs were primarily linked to the leukocyte migration involved in the inflammatory response,the Toll-like receptor signaling pathway,and the TNF signaling pathway.A competing endogenous RNA(ceRNA)network was constructed with 5 differentially expressed circRNAs,5 differentially expressed miRNAs and 42 differentially expressed mRNAs.Among them,hsa_circ_0065336 was found to indirectly regulate PTPN11 expression by sponging miR-505-3p.Conclusions:These data revealed a comprehensive circRNA-associated ceRNA network during T.asahii infection,thus providing new insights into the pathogenesis of the T.asahii-host interactions.