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.
AbstractsBackgroundRhesus macaques living in western Sichuan, China, have been separated into several isolated populations due to habitat fragmentation. Previous studies based on the neutral or nearly neutral markers (mitochondrial DNA or microsatellites) showed high levels of genetic diversity and moderate genetic differentiation in the Sichuan rhesus macaques. Variation at the major histocompatibility complex (MHC) loci is widely accepted as being maintained by balancing selection, even with a low level of neutral variability in some species. However, in small and isolated or bottlenecked populations, balancing selection may be overwhelmed by genetic drift. To estimate microevolutionary forces acting on the isolated rhesus macaque populations, we examined genetic variation at Mhc-DQB1 loci in 119 wild rhesus macaques from five geographically isolated populations in western Sichuan, China, and compared the levels of MHC variation and differentiation among populations with that previously observed at neutral microsatellite markers.Results23 Mamu-DQB1 alleles were identified in 119 rhesus macaques in western Sichuan, China. These macaques exhibited relatively high levels of genetic diversity at Mamu-DQB1. The Hanyuan population presented the highest genetic variation, whereas the Heishui population was the lowest. Analysis of molecular variance (AMOVA) and pairwise FST values showed moderate genetic differentiation occurring among the five populations at the Mhc-DQB1 locus. Non-synonymous substitutions occurred at a higher frequency than synonymous substitutions in the peptide binding region. Levels of MHC variation within rhesus macaque populations are concordant with microsatellite variation. On the phylogenetic tree for the rhesus and crab-eating macaques, extensive allele or allelic lineage sharing is observed betweenthe two species.ConclusionsPhylogenetic analyses confirm the apparent trans-species model of evolution of the Mhc-DQB1 genes in these macaques. Balancing selection plays an important role in sharing allelic lineages between species, but genetic drift may share balancing selection dominance to maintain MHC diversity. Great divergence at neutral or adaptive markers showed that moderate genetic differentiation had occurred in rhesus macaque populations in western Sichuan, China, due to the habitat fragmentation caused by long-term geographic barriers and human activity. The Heishui population should be paid more attention for its lowest level of genetic diversity and relatively great divergence from others.
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