miR-150 duplexによる遺伝子制御 : 肺腺癌において、miR-150-3pはTNS4を制御する

Material type: 博士論文

Author: 美園, 俊祐

Publisher: MDPI

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Material Format: Digital

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Name of awarding university/degree: 鹿児島大学,博士(医学),Doctor of Philosophy in Medical Science

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Note (General)：: 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨Abstract: Based on ourmiRNAexpression signatures, wefocused on miR-150-5p (the guide strand) and miR-150-3p (the pas...

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Material Type: 博士論文
Title: miR-150 duplexによる遺伝子制御 : 肺腺癌において、miR-150-3pはTNS4を制御する
Author/Editor: 美園, 俊祐
Author Heading: 美園, 俊祐ミソノ, シュンスケ
Publication, Distribution, etc.: MDPI
Alternative Title: Molecular Pathogenesis of Gene Regulation by the miR-150 Duplex : miR 150-3p Regulates TNS4 in Lung Adenocarcinoma
Degree grantor/type: 鹿児島大学
Date Granted: 2021-03-25
Dissertation Number: 甲総研第600号
Degree Type: 博士(医学)
Doctor of Philosophy in Medical Science
Text Language Code: eng
Subject Heading: MicroRNA
miR-150-5p
miR-150-3p
lung adenocarcinoma
TNS4
Target Audience: 一般
Note (General): 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨
Abstract: Based on ourmiRNAexpression signatures, wefocused on miR-150-5p (the guide strand) and miR-150-3p (the passenger strand) to investigate their functional significance in lung adenocarcinoma (LUAD). Downregulation of miR-150 duplex was confirmed in LUAD clinical specimens. In vitro assays revealed that ectopic expression of miR-150-5p and miR-150-3p inhibited cancer cell malignancy. We performed genome-wide gene expression analyses and in silico database searches to identify their oncogenic targets in LUAD cells. A total of 41 and 26 genes were identified as miR-150-5p and miR-150-3p targets, respectively, and they were closely involved in LUAD pathogenesis. Among the targets, we investigated the oncogenic roles of tensin 4 (TNS4) because high expression of TNS4 was strongly related to poorer prognosis of LUAD patients (disease-free survival: p = 0.0213 and overall survival: p = 0.0003). Expression of TNS4 was directly regulated by miR-150-3p in LUAD cells. Aberrant expression of TNS4 was detected in LUAD clinical specimens and its aberrant expression increased the aggressiveness of LUAD cells. Furthermore, we identified genes downstream from TNS4 that were associated with critical regulators of genomic stability. Our approach (discovery of anti-tumor miRNAs and their target RNAs for LUAD) will contribute to the elucidation of molecular networks involved in the malignant transformation of LUAD. Shunsuke Misono, Naohiko Seki, Keiko Mizuno, Yasutaka Yamada, Akifumi Uchida, Hiroki Sanada, Shogo Moriya, Naoko Kikkawa, Tomohiro Kumamoto, Takayuki Suetsugu and Hiromasa Inoue Molecular Pathogenesis of Gene Regulation by the miR-150 Duplex: miR-150-3p Regulates TNS4 in Lung Adenocarcinoma Cancers 2019, 11(5), 601 https://doi.org/10.3390/cancers11050601
Format (IMT): application/pdf
Source: Diss_美園_俊祐_ISK600_2020 （fulltext）
https://ir.kagoshima-u.ac.jp/record/15845/files/Diss_%E7%BE%8E%E5%9C%92_%E4%BF%8A%E7%A5%90_ISK600_2020.pdf
Access Restrictions: インターネット公開
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