| Item type |
文献 / Documents(1) |
| 公開日 |
2021-06-09 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
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資源タイプ |
doctoral thesis |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1159/000512575 |
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関連名称 |
10.1159/000512575 |
| 出版タイプ |
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出版タイプ |
NA |
|
出版タイプResource |
http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| タイトル |
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|
タイトル |
S100P Expression via DNA Hypomethylation Promotes Cell Growth in the Sessile Serrated Adenoma/Polyp-Cancer Sequence |
| タイトル別表記 |
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その他のタイトル |
Sessile serrated adenoma/polyp-cancer sequenceにおいてS100Pは遺伝子脱メチル化により発現し、細胞増殖を促進する |
| 著者 |
高橋, 早代
岡本, 耕一
棚橋, 俊仁
フジモト, ショウタ
中川, 忠彦
板東, 正浩
Ma, Beibei
川口, 智之
藤野, 泰輝
三井, 康裕
北村, 晋志
宮本, 弘志
佐藤, 康史
六車, 直樹
坂東, 良美
サトウ, トシロウ
フジモリ, タカヒロ
高山, 哲治
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| 抄録 |
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内容記述 |
Background/Aims: Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor lesion of colon cancer. Although the relevance of DNA hypermethylation in the SSA/P-cancer sequence is well documented, the role of DNA hypomethylation is unknown. We investigated the biological relevance of DNA hypomethylation in the SSA/P-cancer sequence by using 3-dimensional organoids of SSA/P. Methods: We first analyzed hypomethylated genes using datasets from our previous DNA methylation array analysis on 7 SSA/P and 2 cancer in SSA/P specimens. Expression levels of hypomethylated genes in SSA/P specimens were determined by RT-PCR and immunohistochemistry. We established 3-dimensional SSA/P organoids and performed knockdown experiments using a lentiviral shRNA vector. DNA hypomethylation at CpG sites of the gene was quantitated by MassARRAY analysis. Results: The mean number of hypomethylated genes in SSA/P and cancer in SSA/P was 41.6 ± 27.5 and 214 ± 19.8, respectively, showing a stepwise increment in hypomethylation during the SSA/P-cancer sequence. S100P, S100α2, PKP3, and MUC2 were most commonly hypomethylated in SSA/P specimens. The mRNA and protein expression levels of S100P, S100α2, and MUC2 were significantly elevated in SSA/P compared with normal colon tissues, as revealed by RT-PCR and immunohistochemistry, respectively. Among these, mRNA and protein levels were highest for S100P. Knockdown of the S100P gene using a lentiviral shRNA vector in 3-dimensional SSA/P organoids inhibited cell growth by >50% (p < 0.01). The mean diameter of SSA/P organoids with S100P gene knockdown was significantly smaller compared with control organoids. MassARRAY analysis of DNA hypomethylation in the S100P gene revealed significant hypomethylation at specific CpG sites in intron 1, exon 1, and the 5′-flanking promoter region. Conclusion: These results suggest that DNA hypomethylation, including S100P hypomethylation, is supposedly associated with the SSA/P-cancer sequence. S100P overexpression via DNA hypomethylation plays an important role in promoting cell growth in the SSA/P-cancer sequence. |
| キーワード |
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|
主題 |
SSA/P |
| キーワード |
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|
主題 |
DNA hypomethylation |
| キーワード |
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|
主題 |
S100P |
| キーワード |
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|
主題 |
3-dimensional organoid |
| キーワード |
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|
主題 |
Genome-wide DNA methylation array |
| キーワード |
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|
主題 |
Sessile serrated adenoma/polyp |
| 書誌情報 |
en : Digestion
巻 102,
号 5,
p. 789-802,
発行日 2021-01-04
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
00122823 |
| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
14219867 |
| 収録物ID |
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|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA00628636 |
| 収録物ID |
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|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA12781324 |
| 出版者 |
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|
出版者 |
Karger |
| 備考 |
|
|
値 |
内容要旨・審査要旨・論文本文の公開
本論文は，著者Sayo Takahashi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。
学位授与者所属 : 徳島大学大学院医科学教育部（医学専攻） |
| 権利情報 |
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|
権利情報 |
© 2020 S. Karger AG, Basel |
| EID |
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識別子 |
373131 |
| 言語 |
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言語 |
eng |
| 報告番号 |
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学位授与番号 |
甲第3486号 |
| 学位記番号 |
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|
値 |
甲医第1490号 |
| 学位授与年月日 |
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学位授与年月日 |
2021-03-17 |
| 学位名 |
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学位名 |
博士（医学） |
| 学位授与機関 |
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学位授与機関名 |
徳島大学 |
k3486_abstract_review.pdf (254 KB)
