{"id":"3dcd9c11-1990-5e40-a927-fa77ecc2adea","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:folate-ggh-silencing-tail-retention","predicate":"increases","statement":"GGH-targeted siRNA increased long-chain folate-polyglutamate content in HCT116 cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"aabadda7-e906-5b8a-bb12-94049a5271cb","mechanism_event_label":"Less tail trimming increased the retained folate pool.","subject":{"id":"769dec6e-589f-5859-8579-1d9d1cc1082a","slug":"ggh-silencing-hct116","display_name":"GGH silencing in HCT116","entity_type_key":"gene"},"object":{"id":"81c45abb-713d-521f-9854-23288f880831","slug":"folate-polyglutamates","display_name":"Folate polyglutamates","entity_type_key":"chemical_species"},"evidence_count":1,"mechanism_event":{"id":"aabadda7-e906-5b8a-bb12-94049a5271cb","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:folate-ggh-silencing-tail-retention-event","event_type":"biochemical_relationship","label":"Less tail trimming increased the retained folate pool.","description":"GGH-targeted siRNA increased long-chain folate-polyglutamate content in HCT116 cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"769dec6e-589f-5859-8579-1d9d1cc1082a","slug":"ggh-silencing-hct116","display_name":"GGH silencing in HCT116","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"81c45abb-713d-521f-9854-23288f880831","slug":"folate-polyglutamates","display_name":"Folate polyglutamates","entity_type_key":"chemical_species"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6ab9a506-11c6-54d9-b4f1-85a6553a1126","slug":"ggh","display_name":"Human gamma-glutamyl hydrolase / GGH","entity_type_key":"protein"},"role":"silenced enzyme","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"experimental_model","value_text":"GGH-modulated human HCT116 cancer cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Targeted siRNA versus control","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Does not imply universal drug sensitization across folate conditions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"folate","display_name":"Folate (vitamin B9)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Less tail trimming increased the retained folate pool.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[kim2013] γ-Glutamyl hydrolase modulation and folate influence chemosensitivity of cancer cells to 5-fluorouracil and methotrexate (2013). https://pubmed.ncbi.nlm.nih.gov/24045662/ DOI: 10.1038/bjc.2013.579","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HCT116 cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"e1e5574e-4132-5913-bed9-7d96a673522d","evidence_kind":"source_excerpt","locator":"Lines 339-349","start_line":339,"end_line":349,"excerpt":"### folate-ggh-silencing-tail-retention\nGGH-targeted siRNA increased long-chain folate-polyglutamate content in HCT116 cells.\nCondition category: machinery_impairment\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Less tail trimming increased the retained folate pool.\norganism: Homo sapiens\ntissue_or_cell_type: HCT116 cells\nexperimental_model: GGH-modulated human HCT116 cancer cells\nlimitations: Does not imply universal drug sensitization across folate conditions.\nexposure: Targeted siRNA versus control\n[kim2013] γ-Glutamyl hydrolase modulation and folate influence chemosensitivity of cancer cells to 5-fluorouracil and methotrexate (2013). https://pubmed.ncbi.nlm.nih.gov/24045662/ DOI: 10.1038/bjc.2013.579","model_system":"GGH-modulated human HCT116 cancer cells","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [kim2013] γ-Glutamyl hydrolase modulation and folate influence chemosensitivity of cancer cells to 5-fluorouracil and methotrexate (2013). https://pubmed.ncbi.nlm.nih.gov/24045662/ DOI: 10.1038/bjc.2013.579","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"f4ce1a62-9582-5f7a-84f5-a23d0e1bfc68","stable_key":"import-ec174d5a-4903-5745-8646-df0e9d4265e8","title":"Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"e564d43989ece1006c95cd0748e9af6fe369074599a2eebba0a99ebff864b0dd","revision_id":"76674a33-b2a1-5e41-b71b-44399038ff7c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}