治療抵抗性小細胞肺癌におけるmicroRNA発現パターンの解析: miR-30a-3p制御による癌促進遺伝子への影響

• Material Type: 博士論文
• Title: 治療抵抗性小細胞肺癌におけるmicroRNA発現パターンの解析: miR-30a-3p制御による癌促進遺伝子への影響
• Author/Editor: 谷川, 健悟
• Author Heading: 谷川, 健悟 タニガワ, ケンゴ
• Publication, Distribution, etc.: John Wiley & Sons
• Alternative Title: MicroRNA signature of small cell lung cancer after treatment failure: impact on oncogenic targets by miR-30a-3p control
• Degree grantor/type: 鹿児島大学
• Date Granted: 2023-03-10
• Dissertation Number: 甲総研第697号
• Degree Type: 博士(医学); Doctor of Philosophy in Medical Science
• Text Language Code: eng
• Subject Heading: downstream neighbor of SON; microRNA signature; miR-30a-3p; small-cell lung cancer; treatment failure
• 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; Small-cell lung cancer (SCLC) is associated with a high mortality rate and limited treatment efficacy. We created a microRNA (miRNA) expression signature by RNA sequencing using specimens from patients with SCLC who had failed treatment. Forty-nine miRNAs were downregulated in SCLC tissues and were candidate tumor-suppressive miRNAs. In this signature, both guide and passenger strands were downregulated for five miRNAs (miR-30a, miR-34b, miR-34c, miR-223, and miR-4529). Recent studies have revealed that passenger strands of miRNAs are involved in the molecular pathogenesis of human cancer. Although miR-30a-5p (the guide strand) has been shown to be a tumor-suppressive miRNA in various types of cancers, miR-30a-3p (the passenger strand) function is not well characterized in SCLC cells. We investigated the functional significance of miR-30a-3p and oncogenic genes regulated by miR-30a-3p in SCLC cells. Ectopic expression assays showed that miR-30a-3p expression inhibited cell proliferation and induced cell cycle arrest and apoptosis in two SCLC cell lines. Furthermore, in silico database searches and gene expression assays identified 25 genes as putative targets of miR-30a-3p in SCLC cells. Luciferase reporter assays revealed that downstream neighbor of SON (DONSON) was directly regulated by miR-30a-3p in SCLC cells. Knockdown of DONSON induced cell cycle arrest in SCLC cells and DONSON overexpression were detected in SCLC clinical samples. Analyzing the regulatory networks of tumor-suppressive miRNAs may lead to the identification of therapeutic targets in SCLC. Kengo Tanigawa, Shunsuke Misono, Keiko Mizuno, Shunichi Asai, Takayuki Suetsugu, Akifumi Uchida, Minami Kawano, Hiromasa Inoue, Naohiko Seki MicroRNA signature of small-cell lung cancer after treatment failure: impact on oncogenic targets by miR-30a-3p control Molecular Oncology17(2023) 328–343 https://doi.org/10.1002/1878-0261.13339
• Format (IMT): application/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

Table of Contents

Result_TANIGAWA_Kengo_isk_697 other

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Diss_谷川_健悟_ISK697_2022 fulltext

Abstract_谷川_健悟_4520810199_2022 abstract