ID 110157
著者
梶浦, 耕一郎 Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University|Department of Thoracic, Endocrine and Oncological Surgery, Graduate School of Biomedical Sciences, Tokushima University KAKEN研究者をさがす
増田, 清士 Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University KAKEN研究者をさがす
成戸, 卓也 Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University KAKEN研究者をさがす
コウモト, トモヒロ Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University
ワタナベ, ミキ Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University
坪井, 光弘 Department of Thoracic, Endocrine and Oncological Surgery, Graduate School of Biomedical Sciences, Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
滝沢, 宏光 Department of Thoracic, Endocrine and Oncological Surgery, Graduate School of Biomedical Sciences, Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
近藤, 和也 Department of Oncological Medical Services, Graduate School of Biomedical Sciences, Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
丹黒, 章 Department of Thoracic, Endocrine and Oncological Surgery, Graduate School of Biomedical Sciences, Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
井本, 逸勢 Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
キーワード
TRIM58
early-stage lung adenocarcinoma
tumor suppressor gene
methylation
smoking status
資料タイプ
学術雑誌論文
抄録
In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.
掲載誌名
Oncotarget
ISSN
19492553
8
2
開始ページ
2890
終了ページ
2905
並び順
2890
発行日
2016-12-01
備考
Copyright: © 2017 Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
EDB ID
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系
病院