Disease Models & Mechanisms最新文献_第4页

Characteristics of Japanese encephalitis virus infection in NCG-hSTAT2+/+ mice: a novel model for studying neurological symptoms and immune response. 日本脑炎病毒感染NCG-hSTAT2+/+小鼠的特征：研究神经症状和免疫反应的新模型

IF 3.3 3区医学

Disease Models & Mechanisms Pub Date : 2025-08-26 DOI: 10.1242/dmm.052431

Caiqin Zhang, Yiran Li, Yifan Zhou, Yong Zhao, Pengpeng Wu, Bing Bai, Yifan Ma, Jing Qin, Han Meng, Yangchao Dong, Changhong Shi

{"title":"Characteristics of Japanese encephalitis virus infection in NCG-hSTAT2+/+ mice: a novel model for studying neurological symptoms and immune response.","authors":"Caiqin Zhang, Yiran Li, Yifan Zhou, Yong Zhao, Pengpeng Wu, Bing Bai, Yifan Ma, Jing Qin, Han Meng, Yangchao Dong, Changhong Shi","doi":"10.1242/dmm.052431","DOIUrl":"https://doi.org/10.1242/dmm.052431","url":null,"abstract":"Japanese encephalitis virus (JEV), a leading cause of viral encephalitis in Asia and the Western Pacific, is regulated by type I interferon (IFN) signaling pathway, in which STAT2 is critical. However, STAT2's exact role in JEV-mediated IFN evasion remains unclear. Existing murine models of JEV infection predominantly employ high viral titers to induce encephalitis and primarily use immunocompetent or IFN receptor-deficient mice, limiting their utility for studying JEV's IFN evasion mechanisms. To address this, we developed a humanized STAT2 mouse model (NCG-hSTAT2+/+) and infected it with 10³ PFU of JEV-p3. These mice exhibited severe encephalitis resembling clinical human infections, characterized by elevated viral loads, and increased proinflammatory cytokines. Especially, it presents typical neurological symptoms, such as activated astrocytes and distinct neuropathological changes. This suggests that NCG-hSTAT2+/+ mice exhibit higher susceptibility to JEV and more severe neurological symptoms, which is consistent with that observed in clinical patients exhibited. This model significantly advances the study of JEV pathogenesis, therapeutic evaluation, and understanding of human STAT2's role in neuroinvasion and immune evasion.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extended passaging of the SKOV3 ovarian cancer cell line leads to two phenotypically different strains. SKOV3细胞系的延长传代导致两个表型不同的菌株。

IF 3.3 3区医学

Disease Models & Mechanisms Pub Date : 2025-08-01 Epub Date: 2025-08-26 DOI: 10.1242/dmm.052451

Eglė Žymantaitė, Migle Gabrielaite, Vita Pašukonienė, Agata Mlynska

{"title":"Extended passaging of the SKOV3 ovarian cancer cell line leads to two phenotypically different strains.","authors":"Eglė Žymantaitė, Migle Gabrielaite, Vita Pašukonienė, Agata Mlynska","doi":"10.1242/dmm.052451","DOIUrl":"10.1242/dmm.052451","url":null,"abstract":"Continuous passaging of cancer cell lines can drive phenotypic and genotypic divergence, potentially compromising the reliability of such models. In this study, we show that two late-passage strains (S1 and S2) of ovarian cancer cell line SKOV3, although authenticated via short tandem repeat (STR) profiling as identical, exhibit substantial differences in morphology, transcriptomic signatures, ability to form 3D cultures and chemotherapeutic responses. Notably, S1 formed compact 3D spheroids and exhibited enhanced epithelial-mesenchymal transition (EMT) pathway activity, whereas S2 displayed a more proliferative, MYC-driven phenotype with larger spheroid structures requiring higher seeding densities. Transcriptomic analysis revealed pathways associated with hypoxia, EMT and angiogenesis in 3D culture, highlighting the complexity introduced by dimensionality in tumour modelling. Critically, S1 showed higher sensitivity to doxorubicin than S2 (IC50 of 0.12 µM versus 1.28 µM, P=0.0001), indicating how clonal evolution can confound drug-response assays. Ultimately, our findings suggest that although STR profiling remains essential for cell line authentication, functionally distinct subpopulations can arise and coexist within the same culture, and their isolation may reveal divergent phenotypes that compromise reproducibility in preclinical cancer research.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel MAP7D1 mutation causes mitotic defects and RPS14 accumulation in Shwachman-Diamond syndrome patient cells. 一种新的MAP7D1突变导致Shwachman-Diamond综合征患者细胞有丝分裂缺陷和RPS14积累。

IF 3.3 3区医学

Disease Models & Mechanisms Pub Date : 2025-08-01 Epub Date: 2025-08-26 DOI: 10.1242/dmm.052409

Seren Kucukvardar, Arzu Karabay

{"title":"A novel MAP7D1 mutation causes mitotic defects and RPS14 accumulation in Shwachman-Diamond syndrome patient cells.","authors":"Seren Kucukvardar, Arzu Karabay","doi":"10.1242/dmm.052409","DOIUrl":"10.1242/dmm.052409","url":null,"abstract":"The importance of microtubule stability and microtubule-associated proteins in the etiology of Shwachman-Diamond syndrome (SDS) has been highlighted in recent studies. In one patient with SDS, a novel MAP7D1:c.601C>T, p.R201W variant has been identified. In this study, the causality of this variant in the pathogenesis of SDS was investigated. Mutation in the microtubule-binding domain of MAP7D1 caused disruption of its interaction with microtubules. SDS fibroblasts exhibited a decreased cell size with reduced microtubule density, and mitotic defects, including multipolar or bipolar unstable spindles, lagging chromosomes, and shortened inter-centrosomal distance. Additionally, ribosomal protein S14 (RPS14) accumulated within incorrectly dividing SDS fibroblasts. To further evaluate whether these abnormalities are directly attributable to the MAP7D1 mutation, mitotic processes were investigated through genetic manipulations of MAP7D1 in T98G glioblastoma and HEK293T embryonic kidney cell lines. Consistent with data from SDS fibroblasts, similar phenotypes were detected upon overexpression of mutant MAP7D1 and depletion of MAP7D1. Our findings revealed that the MAP7D1 mutation acts as a loss-of-function mutation and contributes to SDS pathogenesis by disrupting microtubule dynamics and ribosomal protein regulation, identifying MAP7D1 as a gene with substantial impact for SDS.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"18 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modeling metastasis - leveraging novel tools to streamline discovery in advanced cancer. 建模转移-利用新工具来简化晚期癌症的发现。

IF 3.3 3区医学

Disease Models & Mechanisms Pub Date : 2025-08-01 Epub Date: 2025-09-03 DOI: 10.1242/dmm.052449

Nicole M Eskow, Eva Hernando

引用次数: 0

Loss of Drosophila ribosomal protein S6 kinase II causes mitochondrial dysfunction and cell death. 果蝇核糖体蛋白S6激酶II缺失导致线粒体功能障碍和细胞死亡。

IF 3.3 3区医学

Disease Models & Mechanisms Pub Date : 2025-08-01 Epub Date: 2025-08-19 DOI: 10.1242/dmm.052374

Ting Deng, Lajos Kalmar, Samantha Loh, Olivier E Pardo, L Miguel Martins

{"title":"Loss of Drosophila ribosomal protein S6 kinase II causes mitochondrial dysfunction and cell death.","authors":"Ting Deng, Lajos Kalmar, Samantha Loh, Olivier E Pardo, L Miguel Martins","doi":"10.1242/dmm.052374","DOIUrl":"10.1242/dmm.052374","url":null,"abstract":"Mitochondria are dynamic organelles that are critical for energy production in high-demand tissues, such as the brain and muscle, with fusion and fission maintaining network integrity. The dysregulation of these processes underlies pathologies, such as neurodegenerative diseases. Ribosomal S6 kinases (RSK1-4) are effectors of extracellular signal-regulated kinases (ERKs), with roles in cell survival and metabolism. Here, we show that RSKs are essential for mitochondrial health. In human cells, siRNAs targeting any RSK isoform (RSK1-4) induced mitochondrial fragmentation and reduced viability. In Drosophila melanogaster, CRISPR-mediated loss of S6kII (the sole RSK orthologue) caused mitochondrial dysfunction and tissue degeneration in high-energy-demand organs, including the indirect flight muscle and brain, accompanied by autophagic activation. Notably, we rescued these defects by expressing human RSK4, underscoring functional conservation. Our findings establish RSKs as critical regulators of mitochondrial integrity, linking ERK signalling to organelle dynamics. This work identifies RSKs as regulators of mitochondrial health in energy-demanding tissues, providing insights into the mechanisms underlying neurodegeneration and strategies to target ERK/RSK-driven mitochondrial dysfunction.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"18 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MSRB3 antioxidant activity is necessary for inner ear cuticular plate structure and hair bundle integrity. MSRB3的抗氧化活性是维持内耳角质层结构和毛束完整性所必需的。

IF 3.3 3区医学

Disease Models & Mechanisms Pub Date : 2025-08-01 Epub Date: 2025-08-19 DOI: 10.1242/dmm.052194

Gowri Nayak, Elodie M Richard, Byung Cheon Lee, Gavin P Riordan, Inna A Belyantseva, Bruno Manta, Thomas B Friedman, Vadim N Gladyshev, Saima Riazuddin

{"title":"MSRB3 antioxidant activity is necessary for inner ear cuticular plate structure and hair bundle integrity.","authors":"Gowri Nayak, Elodie M Richard, Byung Cheon Lee, Gavin P Riordan, Inna A Belyantseva, Bruno Manta, Thomas B Friedman, Vadim N Gladyshev, Saima Riazuddin","doi":"10.1242/dmm.052194","DOIUrl":"10.1242/dmm.052194","url":null,"abstract":"Methionine sulfoxide reductases (MSRs) are enzymes responsible for catalyzing the reduction of methionine sulfoxides. We previously demonstrated that variants in human MSRB3, an MSR family member, are associated with profound autosomal recessive prelingual non-syndromic deafness, DFNB74. To better understand the role of MSRB3 in the auditory pathway, we generated complete Msrb3 gene knockout mice. The Msrb3-deficient mice showed profound deafness by postnatal day 16, which was accompanied by morphological abnormalities including altered stereocilia bundle shape and cuticular plate degeneration, followed by hair cell apoptotic death. Although the absence of MSRB3 primarily affected the actin cytoskeleton, rootlets were present, and the localization of major F-actin stereocilia-core proteins was unaltered. Biochemical assays demonstrated that wild-type MSRB3, but not MSRB3 harboring p.Cys89Gly, the same variant reported for DFNB74, can repolymerize oxidized actin. Consistent with these results, we observed a decreased ratio of reduced/total actin in the inner ears of Msrb3 knockout mice. These data suggest a protective role for MSRB3 in the maintenance and maturation of stereocilia and hair cells, a conserved mechanism aimed at maintaining actin redox dynamics in these sensory cells.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"18 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Uncovering an antifibrotic Prrx1-lineage mesenchymal cell subpopulation in fibrotic lungs. 揭示纤维化肺中抗纤维化prrx1系间充质细胞亚群。

IF 3.3 3区医学

Disease Models & Mechanisms Pub Date : 2025-08-01 Epub Date: 2025-08-26 DOI: 10.1242/dmm.052179

Meline Homps-Legrand, Madeleine Jaillet, Lou Deneuville, Gregory Gautier, Bruno Crestani, Arnaud A Mailleux

{"title":"Uncovering an antifibrotic Prrx1-lineage mesenchymal cell subpopulation in fibrotic lungs.","authors":"Meline Homps-Legrand, Madeleine Jaillet, Lou Deneuville, Gregory Gautier, Bruno Crestani, Arnaud A Mailleux","doi":"10.1242/dmm.052179","DOIUrl":"10.1242/dmm.052179","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a rare and fatal lung disease caused by progressive damage to alveolar epithelial cells, leading to abnormal activation of mesenchymal cells. The PRRX1 transcription factor (TF) has been found to be reactivated in IPF and was previously identified as a key mesenchymal TF in pulmonary fibrosis. In this study, we utilized the Prrx1:CreERT2; Rosa26iTomato murine transgenic line to further characterize the Prrx1-positive cell lineage in healthy and fibrotic lungs. The Prrx1 limb enhancer (Prrx1enh) was undetectable by immunohistochemistry in uninjured lung tissue. However, during the fibrotic phase in the bleomycin model of pulmonary fibrosis, Prrx1enh became activated, marking a population of cells that differentiated into mesenchymal progeny. To investigate further, we conducted reprogramming of these subpopulations after conditional and inducible Prrx1 loss of function. Prrx1 loss in these cells led to worsened fibrosis, indicating that this specific cell population has antifibrotic properties. Our findings reveal a previously unrecognized subpopulation of Prrx1-positive mesenchymal cells that are activated during fibrogenesis. These cells could serve as targets for future therapies aimed at mitigating fibrotic progression in IPF.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"18 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interaction between neuromuscular junction metabolic requirements in fragile X syndrome and glycogen storage disease models. 脆性X综合征和糖原储存病模型在代谢神经肌肉连接需求中的交叉。

IF 3.3 3区医学

Disease Models & Mechanisms Pub Date : 2025-08-01 Epub Date: 2025-09-01 DOI: 10.1242/dmm.052183

Aashi Gurijala, Emma Rushton, Shannon N Leahy, Nichalas Nelson, Charles R Tessier, Kendal Broadie

{"title":"Interaction between neuromuscular junction metabolic requirements in fragile X syndrome and glycogen storage disease models.","authors":"Aashi Gurijala, Emma Rushton, Shannon N Leahy, Nichalas Nelson, Charles R Tessier, Kendal Broadie","doi":"10.1242/dmm.052183","DOIUrl":"10.1242/dmm.052183","url":null,"abstract":"A classic human patient comorbidity of fragile X syndrome and glycogen storage disease type IX has symptoms far more severe than those for either disease alone. Causal variants result in loss of the translational regulator fragile X ribonucleoprotein 1 (FMRP) and metabolic regulator phosphorylase kinase regulatory subunit alpha 2 (PHKA2), respectively. We hypothesized FMRP-PHKA2 interaction based on unsustainably elevated metabolic demand. In Drosophila disease models, single null mutants were viable, but double knockout (DKO) animals exhibited 100% synthetic lethality, showing an essential interaction. Metabolically, dFMRP and dPHKA2 loss alone caused opposing changes in glycogen and fat stores, but DKO animals had both energy stores returned to normal. Regulatory Fat body protein 1 was elevated in single disease models but likewise returned to normal in the DKO animals. In tests of neurological phenotypes, neuromuscular junction mitochondrial function, synapse architecture and neurotransmission strength were all elevated by dFMRP loss, but these synaptic properties were restored to normal levels by co-removal of dPHKA2 in DKO animals. Thus, dFMRP and dPHKA2 strongly interact in metabolic and neuromuscular mechanisms, without explaining the DKO lethal interaction.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The importance of imperfect pre-clinical models in adolescent idiopathic scoliosis. 不完善的临床前模型在青少年特发性脊柱侧凸中的重要性。

IF 3.3 3区医学

Disease Models & Mechanisms Pub Date : 2025-08-01 Epub Date: 2025-09-01 DOI: 10.1242/dmm.052438

Diane S Sepich, Ryan S Gray, Nadav Ahituv, Christina A Gurnett, Jonathan J Rios, Lila Solnica-Krezel, Carol A Wise

{"title":"The importance of imperfect pre-clinical models in adolescent idiopathic scoliosis.","authors":"Diane S Sepich, Ryan S Gray, Nadav Ahituv, Christina A Gurnett, Jonathan J Rios, Lila Solnica-Krezel, Carol A Wise","doi":"10.1242/dmm.052438","DOIUrl":"10.1242/dmm.052438","url":null,"abstract":"Adolescent idiopathic scoliosis (AIS) is a twisting spinal deformity that occurs in otherwise healthy children at the time of rapid pre-pubescent growth. AIS affects ∼3% of children worldwide and is the most common musculoskeletal diagnosis in pediatric populations, posing a significant physiological, psychosocial and financial burden to patients. Genetic predisposition is a clear and major contributor to AIS, and insights from genomic discoveries are inspiring translational studies ultimately aimed at developing novel diagnostics and therapies. Pre-clinical animal models of AIS are now essential to validate human genetic findings, understand gene-by-environment interactions, and speed etiologic and therapeutic discovery. In this Perspective, we highlight the current status of pre-clinical models of AIS and discuss the challenges posed by the nature of the disorder combined with the limitations of standard approaches. Current research suggests that straightforward genetic targeting of orthologous AIS disease genes in vertebrates may not necessarily yield equivalent physiological phenotypes but nevertheless can be utilized to understand disease mechanisms. Longer-term, appropriately complex models are needed to fully recapitulate the human AIS phenotype arising from genetic, physiological and mechanical interactions.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"18 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemoprevention of hepatocellular carcinoma using N-acetylgalactosamine-conjugated siRNAs. 利用galnac - sirna对肝细胞癌进行化学预防。

IF 3.3 3区医学

Disease Models & Mechanisms Pub Date : 2025-08-01 Epub Date: 2025-09-01 DOI: 10.1242/dmm.052370

Gianna Maggiore, Meng-Hsiung Hsieh, Amaey Bellary, Purva Gopal, Lin Li, Jason Guo, David Hsiehchen, Tulin Dadali, Wendy Broom, Martin Maier, Hao Zhu

{"title":"Chemoprevention of hepatocellular carcinoma using N-acetylgalactosamine-conjugated siRNAs.","authors":"Gianna Maggiore, Meng-Hsiung Hsieh, Amaey Bellary, Purva Gopal, Lin Li, Jason Guo, David Hsiehchen, Tulin Dadali, Wendy Broom, Martin Maier, Hao Zhu","doi":"10.1242/dmm.052370","DOIUrl":"10.1242/dmm.052370","url":null,"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.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0