Cache Domain Containing 1 Is a Novel Marker of Non-Alcoholic Steatohepatitis-Associated Hepatocarcinogenesis
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- Anna Kakehashi
- Department of Molecular Pathology, Graduate School of Medicine, Osaka City University, Abeno-ku 1-4-3 Asahi-machi, Osaka 545-8585, Japan
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- Arpamas Chariyakornkul
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, 110 Inthawarorot Rd., Sri Phum, Muang, Chiang Mai 50200, Thailand
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- Shugo Suzuki
- Department of Molecular Pathology, Graduate School of Medicine, Osaka City University, Abeno-ku 1-4-3 Asahi-machi, Osaka 545-8585, Japan
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- Napaporn Khuanphram
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, 110 Inthawarorot Rd., Sri Phum, Muang, Chiang Mai 50200, Thailand
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- Kumiko Tatsumi
- Department of Molecular Pathology, Graduate School of Medicine, Osaka City University, Abeno-ku 1-4-3 Asahi-machi, Osaka 545-8585, Japan
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- Shotaro Yamano
- Department of Molecular Pathology, Graduate School of Medicine, Osaka City University, Abeno-ku 1-4-3 Asahi-machi, Osaka 545-8585, Japan
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- Masaki Fujioka
- Department of Molecular Pathology, Graduate School of Medicine, Osaka City University, Abeno-ku 1-4-3 Asahi-machi, Osaka 545-8585, Japan
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- Min Gi
- Department of Molecular Pathology, Graduate School of Medicine, Osaka City University, Abeno-ku 1-4-3 Asahi-machi, Osaka 545-8585, Japan
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- Rawiwan Wongpoomchai
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, 110 Inthawarorot Rd., Sri Phum, Muang, Chiang Mai 50200, Thailand
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- Hideki Wanibuchi
- Department of Molecular Pathology, Graduate School of Medicine, Osaka City University, Abeno-ku 1-4-3 Asahi-machi, Osaka 545-8585, Japan
書誌事項
- 公開日
- 2021-03-10
- 資源種別
- journal article
- 権利情報
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- https://creativecommons.org/licenses/by/4.0/
- DOI
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- 10.3390/cancers13061216
- 公開者
- MDPI AG
説明
<jats:p>In the present study, potential molecular biomarkers of NASH hepatocarcinogenesis were investigated using the STAM mice NASH model, characterized by impaired insulin secretion and development of insulin resistance. In this model, 2-days-old C57BL/6N mice were subjected to a single subcutaneous (s.c.) injection of 200 μg streptozotocin (STZ) to induce diabetes mellitus (DM). Four weeks later, mice were administered high-fat diet (HFD) HFD-60 for 14 weeks (STAM group), or fed control diet (STZ group). Eighteen-week-old mice were euthanized to allow macroscopic, microscopic, histopathological, immunohistochemical and proteome analyses. The administration of HFD to STZ-treated mice induced significant fat accumulation and fibrosis development in the liver, which progressed to NASH, and rise of hepatocellular adenomas (HCAs) and carcinomas (HCCs). In 18-week-old animals, a significant increase in the incidence and multiplicity of HCAs and HCCs was found. On the basis of results of proteome analysis of STAM mice HCCs, a novel highly elevated protein in HCCs, cache domain-containing 1 (CACHD1), was chosen as a potential NASH-HCC biomarker candidate. Immunohistochemical assessment demonstrated that STAM mice liver basophilic, eosinophilic and mixed-type altered foci, HCAs and HCCs were strongly positive for CACHD1. The number and area of CACHD1-positive foci, and cell proliferation index in the area of foci in mice of the STAM group were significantly increased compared to that of STZ group. In vitro siRNA knockdown of CACHD1 in human Huh7 and HepG2 liver cancer cell lines resulted in significant inhibition of cell survival and proliferation. Analysis of the proteome of knockdown cells indicated that apoptosis and autophagy processes could be activated. From these results, CACHD1 is an early NASH-associated biomarker of liver preneoplastic and neoplastic lesions, and a potential target protein in DM/NASH-associated hepatocarcinogenesis.</jats:p>
収録刊行物
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- Cancers
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Cancers 13 (6), 1216-, 2021-03-10
MDPI AG
