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Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kajiura, Koichiro Masuda, Kiyoshi Naruto, Takuya Kohmoto, Tomohiro Watabnabe, Miki Tsuboi, Mitsuhiro Takizawa, Hiromitsu Kondo, Kazuya Tangoku, Akira Imoto, Issei |
| Copyright Year | 2017 |
| Abstract | 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. |
| Starting Page | 2890 |
| Ending Page | 2905 |
| Page Count | 16 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.oncotarget.com/index.php?journal=oncotarget&op=download&page=article&path%5B%5D=13761&path%5B%5D=43753 |
| PubMed reference number | 27926516v1 |
| Alternate Webpage(s) | https://doi.org/10.18632/oncotarget.13761 |
| DOI | 10.18632/oncotarget.13761 |
| Journal | Oncotarget |
| Volume Number | 8 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adenocarcinoma of lung (disorder) Azacitidine Carcinogenesis CpG Islands Cultured Cell Line Genes, Suppressor Hypermethylation Methylation Neoplasms Nephroblastoma Smoke Smoking Status TRIM58 gene Tobacco smoking behavior Tumor Suppressor Genes cell growth study of epigenetics |
| Content Type | Text |
| Resource Type | Article |
