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ID 112375
タイトル別表記
microRNA-100/microRNA-125b発現の低下は大腸粘膜下層浸潤癌のリンパ節転移に関与する
Downregulation of microRNA-100/microRNA-125b
著者
藤野, 泰輝 徳島大学大学院医科学教育部(医学専攻) 徳島大学 教育研究者総覧 KAKEN研究者をさがす
Fujimoto, Akiko Tokushima University
キーワード
Cancer invasion
colorectal cancer with submucosal invasion
lymph node metastasis
miR-100
miR-125b
colorectal cancer
miRNA
資料タイプ
学位論文
抄録
A majority of early colorectal cancers (CRCs) with submucosal invasion undergo surgical operation, despite a very low incidence of lymph node metastasis. Our study aimed to identify microRNAs (miRNAs) specifically responsible for lymph node metastasis in submucosal CRCs. MicroRNA microarray analysis revealed that miR-100 and miR-125b expression levels were significantly lower in CRC tissues with lymph node metastases than in those without metastases. These results were validated by quantitative real-time PCR in a larger set of clinical samples. The transfection of a miR-100 or miR-125b inhibitor into colon cancer HCT116 cells significantly increased cell invasion, migration, and MMP activity. Conversely, overexpression of miR-100 or miR-125b mimics significantly attenuated all these activities but did not affect cell growth. To identify target mRNAs, we undertook a gene expression array analysis of miR-100-silenced HCT116 cells as well as negative control cells. The Ingenuity Pathway Analysis, TargetScan software analyses, and subsequent verification of mRNA expression by real-time PCR identified mammalian target of rapamycin (mTOR) and insulin-like growth factor 1 receptor (IGF1R) as direct, and Fas and X-linked inhibitor-of-apoptosis protein (XIAP) as indirect candidate targets for miR-100 involved in lymph node metastasis. Knockdown of each gene by siRNA significantly reduced the invasiveness of HCT116 cells. These data clearly show that downregulation of miR-100 and miR-125b is closely associated with lymph node metastasis in submucosal CRC through enhancement of invasion, motility, and MMP activity. In particular, miR-100 may promote metastasis by upregulating mTOR, IGF1R, Fas, and XIAP as targets. Thus, miR-100 and miR-125b may be novel biomarkers for lymph node metastasis of early CRCs with submucosal invasion.
掲載誌名
Cancer Science
ISSN
13497006
出版者
Japanese Cancer Association|Wiley Publishing Asia Pty Ltd
108
3
開始ページ
390
終了ページ
397
発行日
2016-12-29
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨:LID201705191011.pdf
論文本文:k3025_fulltext.pdf
本論文は,著者Yasuteru Fujino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。
著者の申請により要約(2017-05-19公開)に替えて論文全文を公開(2018-06-14)
権利情報
© 2016 The Authors Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.( https://creativecommons.org/licenses/by-nc/4.0/ )
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3025号
学位記番号
甲医第1329号
学位授与年月日
2017-03-21
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系