Abstract
BackgroundInvasive 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.MethodsRNA 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.ResultsA 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.ConclusionsThese 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.
Highlights
Invasive Trichosporon asahii (T. asahii) infection frequently occurs with a high mortality in immunodeficient hosts, but the pathogenesis of T. asahii infection remains elusive
The results showed that a total of 10,539 unique Circular RNA (circRNA) were identified, among which 4595, 3315 and 4456 circRNAs were identified in the three control samples, and 3422, 4423 and 4091 circRNAs were identified in the three T. asahii-infected samples (Fig. 1a)
We identified a group of genes that participate in the T. asahii-host interaction, and Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that many of the up-regulated genes, including TNF alpha induced protein 3 (TNFAIP3), TNF receptor superfamily member 10d (TNFRSF10D), TNF receptor superfamily member 1A (TNFRSF1A), CD14, interferon alpha and beta receptor subunit 1 (IFNAR1), interferon regulatory factor 5 (IRF5), were enriched in immune-related pathways, suggesting that T. asahii infection can activate a strong antifungal response that contributes to fungal pathogenic progression
Summary
Invasive Trichosporon asahii (T. asahii) infection frequently occurs with a high mortality in immunodeficient hosts, but the pathogenesis of T. asahii infection remains elusive. T. asahii infection is usually associated with superficial mycosis in immunocompetent hosts but can cause invasive infections in immunosuppressed patients. Circular RNAs (circRNAs), a type of endogenous noncoding RNA that are widely distributed in eukaryotic cells and have relatively conserved regulatory functions and tissue-specific and cell-specific expression patterns [4]. With the wide application of RNA sequencing (RNA-seq) technology and the rapid development of circRNA-specific computational tools, various circRNAs have been reported to be involved in the pathogenesis of cancer, neurological disorders, cardiovascular diseases, diabetes mellitus and autoimmune diseases [7,8,9,10,11]. CircRNAs associated with fungal infections have not been reported to date
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