National University Corporation Okayama University
[Okayama University] Discovery of the fourth drug treatment for intractable gallbladder cancer, “nucleic acid drug therapy”! ~MiR-34a-5p, a microRNA that exhibits antitumor effects, was identified in a new gallbladder cancer model using a mini-organ~ ……
February 13, 2024 (Reiwa 6) National University Corporation Okayama University https://www.okayama-u.ac.jp/
[Image 1: https://prtimes.jp/i/72793/2005/resize/d72793-2005-55b0399719f311656de2-0.jpg&s3=72793-2005-b11f8bd280c8957eea0fc58eac78237b-2504×1430.jpg] -Key points of presentation-
Advanced gallbladder cancer is a disease with a poor prognosis, and effective treatments are limited.
Through analysis using a novel mouse-derived gallbladder organoid model, miR-34a-5p was identified as a microRNA (microRNA) that is less expressed in gallbladder cancer organoids than in normal gallbladder organoids. We also confirmed that expression was similarly low. Through experiments using human gallbladder cancer cell lines and gallbladder cancer xenograft models, we revealed that forced overexpression of miR-34a-5p exhibits antitumor effects through cell cycle arrest.
miR-34a-5p replacement therapy for gallbladder cancer is expected to become a powerful new treatment for gallbladder cancer, which is difficult to cure completely.
◆Summary: Takashi Oda, a doctor from the Department of
Gastroenterology, Okayama University Hospital, National University Corporation Okayama University (Headquarters: Kita-ku, Okayama City, President: Yasutomo Nasu) (currently in his fourth year of doctoral course at the Graduate School of Biomedical Sciences), The research group led by Assistant Professor Koichiro Tsutsumi and Professor Motoyuki Otsuka of the Department of Gastroenterology and Hepatology, Faculty of Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, conducted a comprehensive analysis using a new mouse-derived gallbladder organoid model. We identified miR-34a-5p, which was poorly expressed in gallbladder cancer organoids, and further conducted experiments using human-derived gallbladder cancer cell lines and gallbladder cancer xenograft models. We revealed that overexpression of -34a-5p exhibits antitumor effects, and that one of the mechanisms involved is cell cycle inhibition. The results of this research were published in the online version of “Molecular Therapy Oncology”, the official journal of the American Society for Gene and Cell Therapy, at midnight on February 8, 2024 (US Eastern Time).
Nucleic acid drug therapy for gallbladder cancer, which has a poor prognosis, has the potential to become a new treatment in addition to chemotherapy, immunotherapy, and molecular target therapy, which are standard treatments worldwide, and this research will contribute to its progress. It is considered that Please look forward to the continued challenges and changes of Dr. Oda, Assistant Professor Yasushi Tsutsumi, and Okayama University, a regional core and distinctive research university.
[Image 2: https://prtimes.jp/i/72793/2005/resize/d72793-2005-27230aa32817c9388ee2-1.jpg&s3=72793-2005-41308e75d6445c709a993bd327852d9f-800×461.jpg] Figure 1. Gallbladder cancer cell line NOZ was injected subcutaneously into nude mice, and after tumor formation was confirmed, miR-34a-5p was locally administered. Tumor growth was suppressed in the miR-34a-5p administered group (miR-34a-5p mimic) compared to the control group (NC mimic). Furthermore, when CDK6 immunostaining was performed on the excised subcutaneous tumor, it was confirmed that the expression of CDK6 was significantly reduced.
[Image 3: https://prtimes.jp/i/72793/2005/resize/d72793-2005-6dc0eda9d68eabab7956-2.jpg&s3=72793-2005-002f6cd5a06287b3f32a4dce7bb3de90-800×295.jpg] Figure 2. Mechanism of antitumor effect of miR-34a-5p introduction on gallbladder cancer
◆A word from the researchers
-Takashi Oda, doctor-
Chemotherapy options for gallbladder cancer are gradually increasing, but it is still one of the cancers for which there are few treatment options. We revealed that miR-34a-5p, discovered using a gallbladder organoid model, exerts antitumor effects in gallbladder cancer cell lines and gallbladder cancer xenograft models.
We hope that this research will lead to new treatments and help patients suffering from gallbladder cancer.
-Assistant Professor Koichiro Tsutsumi-
By using a new model in which genetic mutations are introduced into gallbladder organoids that mimic living organisms, we believe that we have identified one of the microRNAs that are important for the growth and progression of gallbladder cancer. As a new treatment strategy for intractable gallbladder cancer, we would like to continue to improve it so that it can be applied clinically in the future.
[Image 4: https://prtimes.jp/i/72793/2005/resize/d72793-2005-8b7b12611d284daa59ec-3.jpg&s3=72793-2005-80b15b0252dd63e9573e46337883b724-430×237.jpg] Doctor Takashi Oda and assistant professor Koichiro Tsutsumi (right) ◆Paper information Paper name: MicroRNA-34a-5p – a pivotal therapeutic target in gallbladder cancer Publication paper: Molecular Therapy Oncology Author: Takashi Oda, Koichiro Tsutsumi*, Taisuke Obata, Eijiro Ueta, Tatsuya Kikuchi, Soichiro Ako, Yuki Fujii, Tatsuhiro Yamazaki, Daisuke Uchida, Kazuyuki Matsumoto, Shigeru Horiguchi, Hironari Kato, Hiroyuki Okada, Ryota Chijimatsu, and Motoyuki Otsuka* *: Corresponding author D O I: 10.1016/j.omton.2024.200765 U R L: https://www.cell.
com/molecular-therapy-family/oncology/fulltext/S2950-3299(24)00007-9. ◆Research funding This research was supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (Grant-in-Aid for Scientific Research C/21K07962, Principal
Investigator: Hiroya Kato, Fundamental Research C/22K08032, Principal Investigator: Koichiro Tsutsumi, Fundamental Research B・22H02828, Principal Investigator: Motoyuki Otsuka) and was supported by the 2020 Okayama Health Promotion Foundation Cancer Research Grant.
◆About detailed press release
The fourth drug treatment for refractory gallbladder cancer, “nucleic acid drug therapy,” has been discovered! ~MiR-34a-5p, a microRNA that exhibits antitumor effects, was identified in a new gallbladder cancer model using a mini-organ~
https://www.okayama-u.ac.jp/up_load_files/press_r5/press20240208-1.pdf ◆Reference
・Okayama University Hospital
https://www.okayama-u.ac.jp/user/hospital/
・Okayama University Hospital, Department of Gastroenterology https://www.okayama-u.ac.jp/user/hospital/index114.html
・Okayama University Graduate School of Biomedical Sciences
https://www.mdps.okayama-u.ac.jp/
◆Reference information
・[Okayama University] Identification of microRNA that exhibits antitumor effects against refractory biliary tract cancer –
Expectations as a new therapeutic agent for gemcitabine-resistant biliary tract cancer –
https://prtimes.jp/main/html/rd/p/000001786.000072793.html
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◆Contact information for this matter
Koichiro Tsutsumi, Assistant Professor, Department of
Gastroenterology, Okayama University Hospital
Okayama University Shikata Campus, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558 TEL: 086-235-7219 FAX: 086-225-5991 http://www.okayama-gastro.com/
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