ArticlePLoS pathogens2022
Knockout of liver fluke granulin, Ov-grn-1, impedes malignant transformation during chronic infection with Opisthorchis viverrini.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- From infection to cholangiocarcinoma: Why opisthorchiids break these rules.One health (Amsterdam, Netherlands) · 2026Review
- Toward transgenic multicellular parasites: CRISPR-Cas12a germline editing ofScience advances · 2026Article
- Gene Editing of a Carcinogenic Liver Fluke Tetraspanin Impairs Parasite Surface Biogenesis and Extracellular Vesicle Uptake by Human Host Cells.The Journal of infectious diseases · 2026Article
- CRISPR/Cas genome editing, functional genomics, and diagnostics for parasitic helminths.International journal for parasitology · 2025Review
- Multi-omics reveals the impact of Clonorchis sinensis infection on mouse gut microbiota, metabolomics and transcriptomics.BMC microbiology · 2025Article
- The immune microenvironment of pathogen-associated cancers and current clinical therapeutics.Molecular cancer · 2025Review
- Viruses of parasites: A roadmap toward diagnostic and therapeutic development.PLoS neglected tropical diseases · 2025Review
- Human Alveolar Echinococcosis-A Neglected Zoonotic Disease Requiring Urgent Attention.International journal of molecular sciences · 2025Review
- Applications of CRISPR in Parasitology.Current pharmaceutical biotechnology · 2025Review
- Reinventing type 2 immunity in cancer.Nature · 2025Review
- How Do Trematodes Induce Cancer? A Possible Evolutionary Adaptation of an Oncogenic Agent Transmitted by Flukes.Evolutionary applications · 2025Article
- Mechanistic insights into liver-fluke-induced bile-duct cancer.Trends in parasitology · 2024Review
- CRISPR-based functional genomics for schistosomes and related flatworms.Trends in parasitology · 2024Review
- Transcriptome changes of liver fluke Opisthorchis viverrini in diabetic hamsters.Parasite (Paris, France) · 2024Article
- Current State of Knowledge on Blood and Tissue-Based Biomarkers for Opisthorchis viverrini-induced Cholangiocarcinoma: A Review of Prognostic, Predictive, and Diagnostic Markers.Asian Pacific journal of cancer prevention : APJCP · 2024Review
- Getting off tract: contributions of intraorgan microbiota to cancer in extraintestinal organs.Gut · 2023Review
- Inflammatory cell responses in biliary mucosa duringOpen veterinary journal · 2023Article
- Cancerogenic parasites in veterinary medicine: a narrative literature review.Infectious agents and cancer · 2023Review
- Secreted and surface proteome and transcriptome ofFrontiers in parasitology · 2023Article
- Transgenesis in parasitic helminths: a brief history and prospects for the future.Parasites & vectors · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Infection with the food-borne liver fluke Opisthorchis viverrini is the principal risk factor for cholangiocarcinoma (CCA) in the Mekong Basin countries of Thailand, Lao PDR, Vietnam, Myanmar and Cambodia. Using a novel model of CCA, involving infection with gene-edited liver flukes in the hamster during concurrent exposure to dietary nitrosamine, we explored the role of the fluke granulin-like growth factor Ov-GRN-1 in malignancy. We derived RNA-guided gene knockout flukes (ΔOv-grn-1) using CRISPR/Cas9/gRNA materials delivered by electroporation. Genome sequencing confirmed programmed Cas9-catalyzed mutations of the targeted genes, which was accompanied by rapid depletion of transcripts and the proteins they encode. Gene-edited parasites colonized the biliary tract of hamsters and developed into adult flukes. However, less hepatobiliary tract disease manifested during chronic infection with ΔOv-grn-1 worms in comparison to hamsters infected with control gene-edited and mock-edited parasites. Specifically, immuno- and colorimetric-histochemical analysis of livers revealed markedly less periductal fibrosis surrounding the flukes and less fibrosis globally within the hepatobiliary tract during infection with ΔOv-grn-1 genotype worms, minimal biliary epithelial cell proliferation, and significantly fewer mutations of TP53 in biliary epithelial cells. Moreover, fewer hamsters developed high-grade CCA compared to controls. The clinically relevant, pathophysiological phenotype of the hepatobiliary tract confirmed a role for this secreted growth factor in malignancy and morbidity during opisthorchiasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.