miR-144-3p/miR-451a promotes lymphovascular invasion through repression of PTEN/p19 in rectal neuroendocrine tumors

• Material Type: 博士論文
• Title: miR-144-3p/miR-451a promotes lymphovascular invasion through repression of PTEN/p19 in rectal neuroendocrine tumors
• Author/Editor: Murayama, Noriaki; Okamoto, Koichi; Nakagawa, Tadahiko; Miyoshi, Jinsei; Nishida, Kensei; Kawaguchi, Tomoyuki; Kagemoto, Kaizo; Kitamura, Shinji; Ma, Beibei; Miyamoto, Hiroshi; Muguruma, Naoki; Yano, Mitsuyasu; Tsuneyama, Koichi; Fujimori, Takahiro; Sato, Yasushi; Takayama, Tetsuji
• Author Heading: Murayama, Noriaki; Okamoto, Koichi; Nakagawa, Tadahiko; Miyoshi, Jinsei; Nishida, Kensei; Kawaguchi, Tomoyuki; Kagemoto, Kaizo; Kitamura, Shinji; Ma, Beibei; Miyamoto, Hiroshi; Muguruma, Naoki; Yano, Mitsuyasu; Tsuneyama, Koichi; Fujimori, Takahiro; Sato, Yasushi; Takayama, Tetsuji
• Publication, Distribution, etc.: Journal of Gastroenterology and Hepatology Foundation|Wiley
• Publication Date: 2022-03-24
• Publication Date (W3CDTF): 2022-03-24
• Alternative Title: 直腸神経内分泌腫瘍において、miR-144-3p/miR-451aはPTEN/p19を介して脈管侵襲を促進する
• Periodical title: Journal of Gastroenterology and Hepatology
• No. or year of volume/issue: 37 5
• Volume: 37
• Issue: 5
• Pages: 919-927
• ISSN (Periodical Title): ISSN : 1440-1746
• Degree grantor/type: 徳島大学
• Date Granted: 2022-10-27
• Dissertation Number: 甲第3664号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: 直腸NET; miR-144-3p; miR-451a; PTEN; p19; rectal NET-G1; lymphovascular invasion; miR-144-3p/451a
• Target Audience: 一般
• Note (General): Background and Aim: Although rectal neuroendocrine tumor (NET-G1) have potential metastatic capability, even among small tumors, no predictive biomarker for invasion and metastasis has been reported. We analyzed microRNA (miRNA) expression profiles in rectal NET-G1 tissues with and without lymphovascular invasion (LVI). Moreover, we then investigated their target genes to clarify the mechanism of invasion/metastasis in NET-G1. Methods: miRNA array analysis was performed using 7 rectal NET-G1 tissues with LVI and 7 without LVI. miRNA expression was confirmed by quantitative real-time PCR. A NET cell line H727 was transfected with miRNA mimic or target gene small interfering RNA, and migration and invasion assays were performed. Results: The expression levels of miR-144-3p and miR-451a were significantly higher in NET-G1 with LVI versus without LVI, as determined by miRNA array analysis and RT-qPCR. A significant correlation was observed between miR-144-3p and miR-451a expression levels, strongly suggesting miR144/451 cluster overexpression in NET-G1 with LVI. Bioinformatic analysis of target genes revealed that miR-144-3p and miR-451a directly interact with PTEN and p19 mRNA, respectively. Immunohistochemistry revealed significantly lower expression of PTEN and p19 in NET-G1 tissues with LVI than in those without LVI. The miR-144-3p and miR-451a mimic significantly increased cell migration/invasion capability, respectively. Knockdown of PTEN and p19 induced significant augmentation of cell invasion and migration capability, respectively. Conclusions: Our data suggest that overexpression of miR-144/miR-451 cluster promotes LVI via repression of PTEN and p19 in rectal NET-G1 cells. miR-144/451 cluster may be a novel biomarker for predicting invasion/metastasis in rectal NET-G1.
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1111/jgh.15833
• 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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