microRNA-99a-5pはSMARCD1を標的としてゲムシタビン抵抗性膀胱癌の細胞老化を誘導する

• 資料種別: 博士論文
• タイトル: microRNA-99a-5pはSMARCD1を標的としてゲムシタビン抵抗性膀胱癌の細胞老化を誘導する
• 著者・編者: 玉井, 元規
• 著者標目: 玉井, 元規
• 出版事項: Federation of European Biochemical Societies / John Wiley & Sons Ltd
• 出版年月日等: 2022-10-18
• 出版年（W3CDTF）: 2022-10-18
• 並列タイトル等: microRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1
• 授与機関名: 鹿児島大学
• 授与年月日: 2022-10-18
• 授与年月日（W3CDTF）: 2022-10-18
• 報告番号: 甲総研第673号
• 学位: 博士(医学)
• 本文の言語コード: eng
• 件名標目: bladder cancer; cellular senescence; gemcitabine resistance; miR-99a-5p; SMARCD1
• NDC: 490
• 対象利用者: 一般
• 一般注記: 出版タイプ： VoR; 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; Patients with advanced bladder cancer are generally treated with a combination of chemotherapeutics, including gemcitabine, but the effect is limited due to acquisition of drug resistance. Thus, in this study, we investigated the mechanism of gemcitabine resistance. First, gemcitabine-resistant cells were established and resistance confirmed in vitro and in vivo. Small RNA sequencing analyses were performed to search for miRNAs involved in gemcitabine resistance. miR-99a-5p, selected as a candidate miRNA, was downregulated compared to its parental cells. In gain-of-function studies, miR-99a-5p inhibited cell viabilities and restored sensitivity to gemcitabine. RNA sequencing analysis was performed to find the target gene of miR-99a-5p. SMARCD1 was selected as a candidate gene. Dual-luciferase reporter assays showed that miR-99a-5p directly regulated SMARCD1. Loss-of-function studies conducted with si-RNAs revealed suppression of cell functions and restoration of gemcitabine sensitivity. miR-99a-5p overexpression and SMARCD1 knockdown also suppressed gemcitabine-resistant cells in vivo. Furthermore, β-galactosidase staining showed that miR-99a-5p induction and SMARCD1 suppression contributed to cellular senescence. In summary, tumor-suppressive miR-99a-5p induced cellular senescence in gemcitabine-resistant bladder cancer cells by targeting SMARCD1.Motoki Tamai, Shuichi Tatarano, Shunsuke Okamura, Wataru Fukumoto, Issei Kawakami, Yoichi Osako, Takashi Sakaguchi, Satoshi Sugita, Masaya Yonemori, Yasutoshi Yamada, Masayuki Nakagawa, Hideki Enokida, Hirofumi YoshinomicroRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1Molecular Oncology 16(6), 1329-1346 (2022)https://doi.org/10.1002/1878-0261.13192
• 国立国会図書館永続的識別子: info:ndljp/pid/12509577; https://dl.ndl.go.jp/pid/12509577
• 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）
• 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://hdl.handle.net/10232/00032139
• 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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