Atorvastatin suppresses high-risk colorectal adenomas via reprogramming of lipid metabolism and Inhibition of stemness.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41455776", "kind": "science-record", "revision": 4, "content_hash": "sha256:ccafad2f1358f3bd6b490a20d7d6ae28b1107e3a3444bad2d425ec7750c6db66", "created_at": "2026-11-01T20:31:26Z", "updated_at": "2026-11-01T22:57:39Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Atorvastatin suppresses high-risk colorectal adenomas via reprogramming of lipid metabolism and Inhibition of stemness.", "doi": "10.1038/s41598-025-32406-y", "pmid": "41455776", "authors": ["Wentong Chen", "Mengxiao Ge", "Shuangyi Sun", "Hanxiao Zhang", "Zeqin Wang", "Yumeng Guo", "Zhongguang Luo"], "journal": "Scientific reports", "year": 2025, "abstract": "As critical precursors to colorectal cancer (CRC), high-risk colorectal adenomas (HR-CRAs) lack effective chemopreventive strategies beyond endoscopic resection. We previously established a standardized protocol for culturing patient-derived HR-CRA organoids (HR-CRA-PDOs), creating a robust platform for targeted drug discovery in colorectal premalignancy. Bioinformatics investigation was conducted to unveil the significant dysregulation of lipid metabolism in HR-CRAs. HR-CRA-PDOs were primarily cultured and exposed to gradient concentrations of atorvastatin, with drug responses evaluated with high-throughput and high-content imaging and ATP-based viability assays. Parallel in vivo validation utilized AOM/DSS-induced mouse model under either normal or high-fat diets. Histological and molecular analyses were conducted to evaluate adenoma dynamics, apoptosis, and lipid metabolism-related gene and protein expressions. Bioinformatics analysis of GEO database (GSE100179 and GSE161277) revealed that HR-CRAs are characterized by dysregulated lipid metabolism, particularly through the upregulation of fatty acid metabolism pathways. In vitro, atorvastatin significantly inhibited HR-CRA-PDO growth in a dose-dependent manner via apoptosis induction and proliferation arrest. Mechanistically, atorvastatin treatment led to significant alterations of gene expression in lipid metabolism pathways including ACOX1, ACOX2, FABP2, NRG1, PPAR-α and SREBF1, concomitant with stemness marker suppression in HR-CRA-PDOs. In vivo, atorvastatin markedly reduced CRA burden in AOM-DSS-induced mouse model, particularly demonstrating enhanced efficacy in high-fat diet contexts. This translational study establishes atorvastatin's dual mechanism in metabolic reprogramming and stemness inhibition, suggesting its potential as a therapeutic strategy for CRA prevention and treatment.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes were identified using the limma package (v3.58.1), with inclusion criteria of average expression value > 1, fold change ≥ 1.5, and adjusted p-value < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41455776", "locator": "sections[4] \"Bulk RNA sequencing data processing\" paragraph 2", "quote": "Differentially expressed genes were identified using the limma package (v3.58.1), with inclusion criteria of average expression value > 1, fold change ≥ 1.5, and adjusted p-value < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41455776", "locator": "sections[29] \"Data availability\" paragraph 2", "quote": "The datasets used and analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41455776"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Primary culture of patient-derived adenoma organoids (CRA-PDOs) Ten human adeno", "ppropriate. siRNA-mediated gene knockdown in patient-derived organoids Transient siRNA knockdown of ACOX1", "of ACOX1, FABP2, and SREBF1 was performed in patient-derived HR-CRA organoids to evaluate their functiona"], "order_basis": "paper_text_order:301", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_imaging", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["responses evaluated with high-throughput and high-content imaging and ATP-based viability assays. Parallel in"], "order_basis": "paper_text_order:695", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["in vivo validation utilized AOM/DSS-induced mouse model under either normal or high-fat diets. Histo", "rkedly reduced CRA burden in AOM-DSS-induced mouse model, particularly demonstrating enhanced efficac", "ing and ATP-based viability assays. Parallel in vivo validation utilized AOM/DSS-induced mouse mo", "stemness marker suppression in HR-CRA-PDOs. In vivo, atorvastatin markedly reduced CRA burden in"], "order_basis": "paper_text_order:757", "id": "assay:3"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["were conducted to evaluate adenoma dynamics, apoptosis, and lipid metabolism-related gene and prote", "RA-PDO growth in a dose-dependent manner via apoptosis induction and proliferation arrest. Mechanis", "s determined using the CellTiter-Glo 3D Cell Viability Assay (Promega, G9682) according to the manufactur", "ity after treatment was determined using the CellTiter-Glo 3D Cell Viability Assay (Promega, G9682)"], "order_basis": "paper_text_order:933", "id": "assay:4"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Methods Bulk RNA sequencing data processing Bulk transcriptomic data wer", "nes and regulatory interactions. Single-cell RNA sequencing data processing Single-cell transcriptomic d", "ods Bulk RNA sequencing data processing Bulk transcriptomic data were downloaded from the GEO database (", "l RNA sequencing data processing Single-cell transcriptomic data were obtained from the GEO database (GS"], "order_basis": "paper_text_order:1997", "id": "assay:5"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ntial hub genes and regulatory interactions. Single-cell RNA sequencing data processing Single-cell transcriptomic d"], "order_basis": "paper_text_order:3252", "id": "assay:6"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["changed every other day. The organoids were passaged at a 1:3 ratio digested with TrypLE (Gibco,"], "order_basis": "paper_text_order:6259", "id": "assay:7"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ctamine RNA iMAX (Invitrogen, 13778150). The transfection mixture was seeded into Matrigel domes (Corn", "for 72 h prior to drug treatment. Following transfection, organoids were treated with 25 µM atorvasta", "lution when appropriate. siRNA-mediated gene knockdown in patient-derived organoids Transient siRNA", "in patient-derived organoids Transient siRNA knockdown of ACOX1, FABP2, and SREBF1 was performed in"], "order_basis": "paper_text_order:6348", "id": "assay:8"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["down efficiency was verified by quantitative real-time PCR (qRT-PCR) as described previously. 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