Evidence mapPaperPMID 41877133Full record

ArticleBMC medicine2026

Targeting STE20-type kinase MST3 improves metabolic dysfunction-associated steatohepatitis without affecting hepatocellular carcinoma development in mice.

Jingjing Zhang, Xiangdong Gongye, Lohitesh Kovooru, Emma Andersson, Bernice Asiedu, Manoj Amrutkar, Nadia Gul, Caitlyn Myers, Sheri Booten, Dan Emil Lind and 6 more

Abstract read
In one paragraph

Article in BMC medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Jingjing ZhangDepartment of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Xiangdong GongyeDepartment of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Lohitesh KovooruDepartment of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Emma AnderssonDepartment of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Bernice AsieduDepartment of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Manoj AmrutkarDepartment of Pathology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Nadia GulWallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
Caitlyn MyersWallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
Sheri BootenIonis Pharmaceuticals, Carlsbad, USA.
Dan Emil LindDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Ying XiaDepartment of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Antonio MolinaroDepartment of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Anetta HärtlovaWallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
Per LindahlSahlgrenska Center for Cancer Research, Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Sue MurrayIonis Pharmaceuticals, Carlsbad, USA.
Margit MahlapuuDepartment of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden. margit.mahlapuu@gu.se.

Funding

Avtal om läkarutbildning och Forskning, ALF ALFGBG-1005122Cancerfonden 25 4328Hjärt-Lungfonden 20240589IngaBritt och Arne Lundbergs Forskningsstiftelse LU2023-0006Stiftelsen Assar Gabrielssons Fond FB24-119Svenska Sällskapet för Medicinsk Forskning PG-24-0354The National Science Foundation for Young Scientists of China 82500697Vetenskapsrådet 2025-02538
6 · The paper itself

Abstract

backgroundMetabolic dysfunction-associated steatohepatitis (MASH) is a major precursor of hepatocellular carcinoma (HCC), yet the molecular mechanisms linking steatohepatitis to malignancy remain poorly defined. The STE20-type kinase MST3 associates with hepatocellular lipid droplets and regulates metabolic homeostasis and stress responses in the liver. Here, we investigated whether pharmacologic inhibition of MST3 could attenuate the initiation and progression of MASH-associated HCC in vivo.

methodsThe therapeutic potential of MST3 inhibition was evaluated in a mouse model in which MASH-HCC was induced by a single diethylnitrosamine injection followed by 30 weeks of Western-style diet feeding. Liver tumor burden was assessed after 12, 21, or 30 weeks of treatment with Mst3-targeting antisense oligonucleotide (ASO) or a non-targeting control ASO, and histological, biochemical, and mechanistic analyses were performed in the 30-week cohort. In parallel, proteomic profiling of CRISPR/Cas9-generated MST3 knockout and wild-type Huh7 cells was conducted to gain molecular insight into MST3-regulated pathways.

resultsMst3 ASO therapy had no impact on the onset or aggravation of experimentally induced MASH-associated HCC in mice, despite markedly improving the whole-body metabolic profile and suppressing all key features of MASH. Proteomic profiling of MST3-deficient hepatocytes revealed coordinated activation of mitochondrial and lysosomal pathways, consistent with enhanced fatty acid degradation and catabolic clearance.

conclusionsOur findings in the selected mouse model of MASH-HCC suggest that MST3 is dispensable for hepatocarcinogenesis, yet its antagonism dampens diet-induced metabolic dysfunction and effectively attenuates MASH severity, challenging the prevailing assumption that targeting MASH driver genes alone is sufficient to prevent HCC development in the context of obesity.

Indexed as

Carcinoma, HepatocellularFatty LiverLiver NeoplasmsProtein Serine-Threonine KinasesAnimalsDiethylnitrosamineDisease Models, AnimalHippo KinasesHumansMaleMiceMice, Inbred C57BLOligonucleotides, AntisenseSerine-Threonine Kinase 3DiethylnitrosamineHippo KinasesOligonucleotides, AntisenseProtein Serine-Threonine KinasesSerine-Threonine Kinase 3Antisense oligonucleotide therapyHepatocellular carcinomaMetabolic dysfunction-associated steatohepatitisMST3

Identifiers

PMID41877133
PMCPMC13063862

What Socratic holds

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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 Socratic graph.