Identification of potential target genes of the trematode transport RNA-derived small RNAs among differentially expressed genes of human monocytes

RNA interference is an evolutionarily conserved mechanism of post-transcriptional gene expression regulation present in all living organisms. It is highly relevant to multiple areas of molecular medicine, including diagnostics and novel immunomodulatory approaches. Recent studies have increasingly highlighted the role of extracellular vesicles and their cargo in parasite-host interactions. The trematode Opisthorchis felineus, which parasitizes the human biliary tract, causes opisthorchiasis, a disease associated with chronic inflammation and other hepatobiliary injuries. The long-term survival of the parasite is likely linked to modulation of host immune response. Nevertheless, the mechanism by which liver fluke vesicles affect human immune cells remains unclear. The aim of this study was to identify potential human gene targets of tRNA-derived small RNAs and to assess their enrichment among differentially expressed genes (DEGs) in the transcriptome of THP-1 human monocytes. Target prediction for eight most abundant O. felineus tRNA fragments identified 1,299 potential target genes in human monocytes. Seven cDNA libraries prepared from THP-1 monocytes  before and after treatment with vesicles from adult O. felineus were sequenced using paired-end 2 × 150 bp sequencing (DNBseq, BGI), yielding 43.8 million reads per library. Among 1484 DEGs, 159 predicted targets of tRNA-derived small RNAs showed significant expression changes upon vesicle treatment. These genes were associated with pathways involved in cell-cycle regulation and cell death, including DNA integrity control (M16357), G1/S transition (M2074), apoptosis (M15303), and programmed cell death (M27436), as well as immune-related pathways, including the monocyte pathway (M4956), mononuclear macrophage differentiation (M25144), MHC-I antigen presentation (M1066), and proteasomemediated antigen processing (M1070). These findings suggests that O. felineus tRNA-derived small RNAs may contribute to the regulation of these processes in human monocytes.

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