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ID 113284
タイトル別表記
ZNF350プロモーターのメチル化は大腸がん細胞の遊走を促進する
著者
田中, 裕基 徳島大学大学院医科学教育部(医学専攻)
西川, 達哉 Tokushima University
キーワード
DNA methylation
EMT
cell migration
ZNF350
colon cancer cells
資料タイプ
学位論文
抄録
Diversification of transcriptomic and epigenomic states may occur during the expansion of colorectal cancers. Certain cancer cells lose their epithelial characters and gain mesenchymal properties, known as epithelial-mesenchymal transition (EMT), and they aggressively migrate into the non-tumorigenic extracellular matrix. In this study, we isolated a subpopulation with accelerated baseline motility (MG cells) and an immotile one (non-MG cells) from a colon cancer cell line (HCT116). Gene expression signatures of the MG cells indicated that this subpopulation was likely an EMT hybrid. The MG cells substantially lost their migratory properties after treatment with a methyltransferase inhibitor, 5-azacytidine, suggesting a role of DNA methylation in this process. Global transcriptome assays of both types of cells with or without 5-azacytidine treatment identified 640 genes, whose expression might be methylation-dependently down-regulated in the MG cells. Global methylation analysis revealed that 35 out of the 640 genes were hyper-methylated in the MG cells. Among them, we focused on the anti-oncogene ZNF350, which encodes a zinc-finger and BRCA1-interacting protein. Notably, ZNF350 knockdown accelerated migration of the non-MG cells, while overexpression of ZNF350 in the MG cells significantly impaired their migration. Finally, pyrosequence analysis together with dual luciferase assays of serially truncated fragments of the ZNF350 promoter (-268 to +49 bp) indicated that three hyper-methylated sites were possibly responsible for the basal promoter activity of ZNF350. Taken together, our results suggest that hyper-methylation of the ZNF350 proximal promoter may be one of the crucial determinants for acquiring increased migratory capabilities in colon cancer cells.
掲載誌名
Oncotarget
ISSN
19492553
出版者
Impact Journals, LLC
9
95
開始ページ
36750
終了ページ
36769
発行日
2018-12-04
備考
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Hiroki Tanakaの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
Copyright: Tanaka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.(https://creativecommons.org/licenses/by/3.0/)
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3257号
学位記番号
甲医第1406号
学位授与年月日
2019-02-28
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系