Abstract
Liver flukes Fasciola hepatica, Opisthorchis viverrini and Clonorchis sinensis are causing agents of liver and hepatobiliary diseases. A remarkable difference between such worms is the fact that O. viverrini and C. sinensis are carcinogenic organisms whereas F. hepatica is not carcinogenic. The release of secretory factors by carcinogenic flukes seems to contribute to cancer development however if some of these target the host cell nuclei is unknown. We investigated the existence of O. viverrini and C. sinensis secretory proteins that target the nucleus of host cells and compared these with the corresponding proteins predicted in F. hepatica. Here we applied an algorithm composed by in silico approaches that screened and analyzed the potential genes predicted from genomes of liver flukes. We found 31 and 22 secretory proteins that target the nucleus of host cells in O. viverrini and C. sinensis, respectively, and that have no homologs in F. hepatica. These polypeptides have enriched the transcription initiation process and nucleic acid binding in O. viverrini and C. sinensis, respectively. In addition, other 11 secretory proteins of O. viverrini and C. sinensis, that target the nucleus of host cells, had F. hepatica homologs, have enriched RNA processing function. In conclusion, O. viverrini and C. sinensis have 31 and 22 genes, respectively, that may be involved in their carcinogenic action through a direct targeting on the host cell nuclei.
Highlights
Liver infections caused by flukes or trematodes, termed parasitic flatworms, are considered a serious global public health problem with over 60 million people infected around the world and above 10% population at risk of these infections (Fürst et al, 2012a; Prasad et al, 2011)
F. hepatica had more potential genes predicted from the genome (n 1⁄4 16830) than O. viverrini (n 1⁄4 16356) and C. sinensis (n 1⁄4 13634)
We identified through Biomart those nuclear targeting proteins that were unique either to O. viverrini or C. sinensis and that had no orthologs in F. hepatica
Summary
Liver infections caused by flukes or trematodes, termed parasitic flatworms, are considered a serious global public health problem with over 60 million people infected around the world and above 10% population at risk of these infections (Fürst et al, 2012a; Prasad et al, 2011) The burden of these infections in the world is widely distributed with high prevalence rates in Asia and South America (Marcos et al, 2007; Parkinson et al, 2007; Machicado et al, 2016) whereas other regions have less prevalence rates (Saijuntha et al, 2019). The mechanism of carcinogenesis displayed by these worms is multifactorial and it comprises the mechanical irritation of biliary tissue, the chronic tissue inflammation and the toxic action of secreted factors (Buisson, 2007) Secreted mitogens such as Ov-GRN-1 by O. viverrini stimulate cell proliferation, angiogenesis and wound repair (Smout et al, 2015). Whether some O. viverrini or C. sinensis proteins target the nucleus of the host cell is unknown
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