title: Hypothetical granulin-like molecule from Fasciola hepatica identified by bioinformatics analysis.
abstract: Fasciola hepatica is considered an emergent human pathogen, causing liver fibrosis or cirrhosis, conditions that are known to be direct causes of cancer. Some parasites have been categorized by WHO as carcinogenic agents such as Opisthorchis viverrini, a relative of F. hepatica. Although these two parasites are from the same class (Trematoda), the role of F. hepatica in carcinogenesis is unclear. We hypothesized that F. hepatica might share some features with O. viverrini and to be responsible to induce proliferation of host cells. We analyzed the recently released genome of F. hepatica looking for a gene coding a granulin-like growth factor, a protein secreted by O. viverrini (Ov-GRN-1), which is a potent stimulator of proliferation of host cells. Using computational biology tools, we identified a granulin-like molecule in F. hepatica, here termed FhGLM, which has high sequence identity level to Ov-GRN-1 and human progranulin. We found evidence of an upstream promoter compatible with the expression of FhGLM. The FhGLM architecture showed to have five granulin domains, one of them, the domain 3, was homologue to Ov-GRN-1 and human GRNC. The structure of the FhGLM granulin domain 3 resulted to have the overall folding of its homologue the human GRNC. Our findings show the presence of a homologue of a potent modulator of cell growth in F. hepatica that might have, as other granulins, a proliferative action on host cells during fascioliasis. Future experimental assays to demonstrate the presence of FhGLM in F. hepatica are needed to confirm our hypothesis.
authors.affiliation: Bioinformatics Laboratory, Department of Cellular and Molecular Sciences, Faculty of Sciences and Philosophy, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, Lima 31, Peru ; Institute for Biocomputation and Physics of Complex Systems, University of Zaragoza, Mariano Esquillo, Edificio I+D, 50018 Saragossa, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Machicado
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Stony Brook University, Stony Brook, 100 Nicolls Road, Stony Brook, NY 11790 USA ; Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 262, Lima 31, Peru.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Marcos
authors.affiliation: Bioinformatics Laboratory, Department of Cellular and Molecular Sciences, Faculty of Sciences and Philosophy, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, Lima 31, Peru.
authors.forename: Mirko
authors.initials: M
authors.lastname: Zimic
keywords: Carcinogenesis; Fasciola; Granulin; Helminth; Homology; Proliferation