ID 110157
Author
Kajiura, Koichiro 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 Search Researchers
Masuda, Kiyoshi Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University KAKEN Search Researchers
Naruto, Takuya Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University KAKEN Search Researchers
Kohmoto, Tomohiro Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University
Watanabe, Miki Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University
Tsuboi, Mitsuhiro Department of Thoracic, Endocrine and Oncological Surgery, Graduate School of Biomedical Sciences, Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Takizawa, Hiromitsu Department of Thoracic, Endocrine and Oncological Surgery, Graduate School of Biomedical Sciences, Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Kondo, Kazuya Department of Oncological Medical Services, Graduate School of Biomedical Sciences, Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Tangoku, Akira Department of Thoracic, Endocrine and Oncological Surgery, Graduate School of Biomedical Sciences, Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Imoto, Issei Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
TRIM58
early-stage lung adenocarcinoma
tumor suppressor gene
methylation
smoking status
Content Type
Journal Article
Description
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.
Journal Title
Oncotarget
ISSN
19492553
Volume
8
Issue
2
Start Page
2890
End Page
2905
Sort Key
2890
Published Date
2016-12-01
Remark
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
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Medical Sciences
University Hospital