食道扁平上皮癌において、腫瘍抑制性microRNA-375はMMP13を制御し腫瘍細胞の遊走能・浸潤能を著明に抑制する。

• Material Type: 博士論文
• Title: 食道扁平上皮癌において、腫瘍抑制性microRNA-375はMMP13を制御し腫瘍細胞の遊走能・浸潤能を著明に抑制する。
• Author/Editor: 大迫, 祐作
• Author Heading: 大迫, 祐作 オオサコ, ユウサク
• Publication, Distribution, etc.: Spandidos Publications
• Publication Date: 2016
• Publication Date (W3CDTF): 2016
• Alternative Title: Regulation of MMP13 by antitumor microRNA-375 markedly inhibits cancer cell migration and invasion in esophageal squamous cell carcinoma.
• Periodical title: International Journal of Oncology
• No. or year of volume/issue: 49 6
• Volume: 49
• Issue: 6
• Pages: 2255-2264
• Degree grantor/type: 鹿児島大学
• Date Granted: 2019-03-19
• Dissertation Number: 甲総研第496号
• Degree Type: 博士(医学); Doctor of Philosophy in Medical Science
• Text Language Code: eng
• Subject Heading: microRNA; miR-375; esophageal squamous cell carcinoma; matrix metalloproteinase 13; tumor suppressor
• Target Audience: 一般
• Note (General): 博士論文本文, 最終試験結果の要旨, 論文審査の要旨, 博士論文要旨; Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies. Recently developed molecular targeted therapies are not available for patients with ESCC. After curative surgical resection, patients frequently suffer distant metastasis and recurrence. Exploration of novel ESCC metastatic pathways may lead to the development of new treatment protocols for this disease. Accordingly, we have sequentially identified microRNA (miRNA)-mediated metastatic pathways in several cancers. Our past studies of miRNA expression signatures have shown that microRNA-375 (miR-375) is frequently reduced in several types of cancers, including ESCC. In the present study, we aimed to investigate novel miR-375-mediated metastatic pathways in ESCC cells. The expression of miR-375 was downregulated in ESCC tissues, and ectopic expression of this miRNA markedly inhibited cancer cell migration and invasion, suggesting that miR-375 acted as an antimetastatic miRNA in ESCC cells. Our strategies for miRNA target searching demonstrated that matrix metalloproteinase 13 (MMP13) was directly regulated by miR-375 in ESCC cells. Overexpression of MMP13 was observed in ESCC clinical tissues, and the expression of MMP13 promoted cancer cell aggressiveness. Moreover, oncogenic genes, including CENPF, KIF14 and TOP2A, were shown to be regulated downstream of MMP13. Taken together, these findings demonstrated that the antitumor miR-375/oncogenic MMP13 axis had a pivotal role in ESCC aggressiveness.These results provide novel insights into the potential mechanisms of ESCC pathogenesis.
• Format (IMT): application/pdf
• Source: Diss_大迫_祐作_ISK496_2018 （fulltext）; https://ir.kagoshima-u.ac.jp/record/14631/files/Diss_%E5%A4%A7%E8%BF%AB_%E7%A5%90%E4%BD%9C_ISK496_2018.pdf
• Access Restrictions: インターネット公開
• Related Material: International Journal of Oncology; https://www.spandidos-publications.com/ijo
• Related Material (DOI): 10.3892/ijo.2016.3745
• 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): 鹿児島大学 : 鹿児島大学リポジトリ