ID | 66556 |
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Author |
Obata, Taisuke
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
Tsutsumi, Koichiro
Department of Gastroenterology and Hepatology, Okayama University Hospital
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Ueta, Eijiro
Department of Gastroenterology and Hepatology, Okayama University Hospital
Oda, Takashi
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
Kikuchi, Tatsuya
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
Ako, Soichiro
Department of Gastroenterology and Hepatology, Okayama University Hospital
Fujii, Yuki
Department of Gastroenterology and Hepatology, Okayama University Hospital
Yamazaki, Tatsuhiro
Department of Gastroenterology and Hepatology, Okayama University Hospital
Uchida, Daisuke
Department of Gastroenterology and Hepatology, Okayama University Hospital
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Matsumoto, Kazuyuki
Department of Gastroenterology and Hepatology, Okayama University Hospital
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Horiguchi, Shigeru
Department of Gastroenterology and Hepatology, Okayama University Hospital
Kato, Hironari
Department of Gastroenterology and Hepatology, Okayama University Hospital
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Okada, Hiroyuki
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
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Otsuka, Motoyuki
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science
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Abstract | Gemcitabine is an effective chemotherapeutic agent for biliary tract cancers (BTCs), including gallbladder cancer (GBC) and cholangiocarcinoma (CCA). However, few other effective agents are currently available, particularly for GEM-refractory BTCs. We previously identified microRNA-451a (miR-451a) as a potential therapeutic target in GBC. To elucidate the antineoplastic effects of miR-451a and its underlying mechanisms, we transfected miR-451a into GBC, gemcitabine-resistant GBC (GR-GBC), and gemcitabine-resistant CCA (GR-CCA) cell lines. Furthermore, mimicking in vivo conditions, tumorigenic GBC organoids and three-dimensional (3D) cell culture systems were employed to investigate the anti-proliferative effects of miR-451a on BTCs, and its effect on stem cell properties. We found that miR-451a significantly inhibited cell proliferation, induced apoptosis, and reduced chemoresistant phenotypes, such as epithelial-mesenchymal transition, in both GBC and GR-GBC. The principal mechanism is probably the negative regulation of the phosphatidylinositol 3-kinase/AKT pathway, partially accomplished by directly downregulating macrophage migration inhibitory factor. The Gene Expression Omnibus database revealed that miR-451a was the most significantly downregulated microRNA in CCA tissues. The introduction of miR-451a resulted in similar antineoplastic effects in GR-CCA. Furthermore, miR-451a reduced cell viability in 3D spheroid models and tumorigenic GBC organoids. These findings suggest that the supplementation of miR-451a is a potential treatment strategy for GEM-refractory BTCs.
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Published Date | 2023-12-12
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Publication Title |
Molecular Therapy Nucleic Acids
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Volume | volume34
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Publisher | Cell Press
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Start Page | 102054
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ISSN | 2162-2531
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © 2023 The Author(s).
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File Version | publisher
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Related Url | isVersionOf https://doi.org/10.1016/j.omtn.2023.102054
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License | http://creativecommons.org/licenses/by-nc-nd/4.0/
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Funder Name |
Japan Society for the Promotion of Science
Okayama Health Foundation
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助成番号 | 21K07962
22K08032
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