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

• 資料種別: 博士論文
• ISSN: 1349-7006
• タイトル: Downregulation of microRNA-100/microRNA-125b is associated with lymph node metastasis in early colorectal cancer with submucosal invasion
• 巻次・部編番号: 108 3
• 著者・編者: 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
• 著者標目: 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
• 出版事項: Japanese Cancer Association|Wiley Publishing Asia Pty Ltd
• 出版年月日等: 2016-12-29
• 出版年（W3CDTF）: 2016-12-29
• 並列タイトル等: 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
• タイトル（掲載誌）: Cancer Science
• 授与機関名: 徳島大学
• 授与年月日: 2017-03-21
• 授与年月日（W3CDTF）: 2017-03-21
• 報告番号: 甲第3025号
• 学位: 博士（医学）
• 博論授与番号: 甲第3025号
• 本文の言語コード: eng
• 件名標目: Cancer invasion; colorectal cancer with submucosal invasion; lymph node metastasis; miR-100; miR-125b; colorectal cancer; miRNA
• 対象利用者: 一般
• 一般注記: 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.
• DOI: info:doi/10.1111/cas.13152; https://doi.org/info:doi/10.1111/cas.13152
• 国立国会図書館永続的識別子: info:ndljp/pid/11115930; https://dl.ndl.go.jp/pid/11115930
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2018-07-03T21:49:10+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: http://repo.lib.tokushima-u.ac.jp/112375
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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2019-09-09 再収集