Downregulation of microRNA-100/microRNA-125b is associated with lymph node metastasis in early colorectal cancer with submucosal invasion

• Material Type: 博士論文
• Title: Downregulation of microRNA-100/microRNA-125b is associated with lymph node metastasis in early colorectal cancer with submucosal invasion
• Author/Editor: Fujino, Yasuteru; Takeishi, Shunsaku; Nishida, Kensei; Okamoto, Koichi; Muguruma, Naoki; Kimura, Tetsuo; Kitamura, Shinji; Miyamoto, Hiroshi; Fujimoto, Akiko; Higashijima, Jun; Shimada, Mitsuo; Rokutan, Kazuhito; Takayama, Tetsuji
• Author Heading: Fujino, Yasuteru; Takeishi, Shunsaku; Nishida, Kensei; Okamoto, Koichi; Muguruma, Naoki; Kimura, Tetsuo; Kitamura, Shinji; Miyamoto, Hiroshi; Fujimoto, Akiko; Higashijima, Jun; Shimada, Mitsuo; Rokutan, Kazuhito; Takayama, Tetsuji
• Publication, Distribution, etc.: Japanese Cancer Association|Wiley Publishing Asia Pty Ltd
• Publication Date: 2016-12-29
• Publication Date (W3CDTF): 2016-12-29
• Alternative Title: 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
• Periodical title: Cancer Science
• No. or year of volume/issue: 108 3
• Volume: 108
• Issue: 3
• Pages: 390-397
• ISSN (Periodical Title): ISSN : 1349-7006
• Degree grantor/type: 徳島大学
• Date Granted: 2017-03-21
• Dissertation Number: 甲第3025号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Cancer invasion; colorectal cancer with submucosal invasion; lymph node metastasis; miR-100; miR-125b; colorectal cancer; miRNA
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): © 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/ )
• Related Material (DOI): 10.1111/cas.13152
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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