Oncogenic Runx1–Myc axis in p53-deficient thymic lymphoma

Material type: 博士論文

Author: 伊達, 悠貴

Publisher: Elsevier B.V.

Publication date: 2022-03-02

Material Format: Digital

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Name of awarding university/degree: Nagasaki University (長崎大学),博士(歯学)

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Note (General)：: p53 deficiency and Myc dysregulation are frequently associated with cancer. However, the molecular mechanisms linking these two major oncogenic events...

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http://hdl.handle.net/10069/00041404

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Material Type: 博士論文
Title: Oncogenic Runx1–Myc axis in p53-deficient thymic lymphoma
Author/Editor: 伊達, 悠貴
Author Heading: 伊達, 悠貴
Publication, Distribution, etc.: Elsevier B.V.
Publication Date: 2022-03-02
Publication Date (W3CDTF): 2022-03-02
Alternative Title: p53欠損性胸腺リンパ腫においてRunx1-Mycは発がん機軸である
Periodical title: Gene
No. or year of volume/issue: 819
Volume: 819
Pages: 146234-
ISSN (Periodical Title): ISSN : 0378-1119
Degree grantor/type: Nagasaki University (長崎大学)
Date Granted: 2022-03-02
Dissertation Number: 甲医歯薬第1401号
Degree Type: 博士(歯学)
Text Language Code: eng
Subject Heading: p53
Myc
Runx1
Lymphoma
Target Audience: 一般
Note (General): p53 deficiency and Myc dysregulation are frequently associated with cancer. However, the molecular mechanisms linking these two major oncogenic events are poorly understood. Using an osteosarcoma model caused by p53 loss, we have recently shown that Runx3 aberrantly upregulates Myc via mR1, a Runx consensus site in the Myc promoter. Here, we focus on thymic lymphoma, a major tumour type caused by germline p53 deletion in mice, and examine whether the oncogenic Runx–Myc axis plays a notable role in the development of p53-deficient lymphoma. Mice lacking p53 specifically in thymocytes (LP mice) mostly succumbed to thymic lymphoma. Runx1 and Myc were upregulated in LP mouse lymphoma compared with the normal thymus. Depletion of Runx1 or Myc prolonged the lifespan of LP mice and suppressed lymphoma development. In lymphoma cells isolated from LP mice, knockdown of Runx1 led to Myc suppression, weakening their tumour forming ability in immunocompromised mice. The mR1 locus was enriched by both Runx1 and H3K27ac, an active chromatin marker. LP mice with mutated mR1 had a longer lifespan and a lower incidence of lymphoma. Treatment with AI-10-104, a Runx inhibitor, improved the survival of LP mice. These results suggest that Myc upregulation by Runx1 is a key event in p53-deficient thymic lymphoma development and provide a clinical rationale for targeting the Runx family in p53-deficient malignancies.
長崎大学学位論文学位記番号:博(医歯薬)甲第1401号学位授与年月日:令和4年3月2日
Author: Yuki Date, Ichiro Taniuchi, Kosei Ito
Citation: Gene, 819, art.no. 146234; 2022
identifier:Nagasaki University (長崎大学), 博士(歯学) (2022-03-02)
Source: fulltext
https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27363&item_no=1&attribute_id=70&file_no=1
Access Restrictions: インターネット公開
Related Material: http://hdl.handle.net/10069/00041404
Related Material (DOI): 10.1016/j.gene.2022.146234
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 長崎大学 : 長崎大学学術研究成果リポジトリ