{"doi":"10.1242/dmm.052370","title":"Chemoprevention of hepatocellular carcinoma using N-acetylgalactosamine-conjugated siRNAs","abstract":"The ability to prevent hepatocellular carcinoma (HCC) in patients with chronic liver disease remains an unmet clinical need. We performed a head-to-head comparison of N-acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA)-mediated inhibition of five genes (CDK1, PD-L1, CTNNB1, SMYD3, ANLN) to prevent cancer in four distinct autochthonous HCC mouse models. siRNA targeting Cdk1 and Anln (siCdk1 and siAnln, respectively) increased overall survival in the CTNNB1/MYC hydrodynamic transfection (HDT) model, in which HCC formation is driven by oncogenes. Both long-term and transient dosing of siCtnnb1 or siAnln prevented cancer development in the NRASG12V/shp53-driven HDT model. siCdk1 and siAnln prevented cancer in a diethylnitrosamine/phenobarbital model, in which tumor formation is driven by mutagenesis and chemical injury. Moreover, siCtnnb1 and siAnln decreased cancer development in a metabolic dysfunction-associated steatohepatitis (MASH) model driven by a Western diet and carbon tetrachloride (CCl4). Given that the use of siAnln was effective in several models, we validated Anln effects using Cre-lox and found that histologic features of MASH and HCC development were independently reduced. This demonstrates that siRNAs are safe and effective in preventing HCC in a large panel of preclinical cancer models, and identifies ANLN as an effective chemoprevention target.","journal":"Disease Models & Mechanisms","year":2025,"id":541883,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9677,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1204529,"name":"Meng-Hsiung Hsieh","orcid":"0000-0001-9791-1318","position":1,"is_corresponding":false},{"id":1378844,"name":"Amaey Bellary","orcid":null,"position":2,"is_corresponding":false},{"id":395730,"name":"Purva Gopal","orcid":"0000-0001-7125-695X","position":3,"is_corresponding":false},{"id":395728,"name":"Lin Li","orcid":"0000-0002-6798-023X","position":4,"is_corresponding":false},{"id":684770,"name":"Jason Guo","orcid":"0000-0003-0062-5118","position":5,"is_corresponding":false},{"id":303628,"name":"David Hsiehchen","orcid":null,"position":6,"is_corresponding":false},{"id":443049,"name":"Tulin Dadali","orcid":null,"position":7,"is_corresponding":false},{"id":1024877,"name":"Wendy Broom","orcid":null,"position":8,"is_corresponding":false},{"id":604767,"name":"Martin A. Maier","orcid":"0000-0002-4987-0184","position":9,"is_corresponding":false},{"id":264169,"name":"Hao Zhu","orcid":"0000-0002-8417-9698","position":10,"is_corresponding":false},{"id":909658,"name":"Gianna Maggiore","orcid":null,"position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:52:51.593043Z","pmid":"40704506","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}