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

• Material Type: 博士論文
• Title: 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
• Author/Editor: 玉井, 元規
• Author Heading: 玉井, 元規
• Publication, Distribution, etc.: Federation of European Biochemical Societies / John Wiley & Sons Ltd
• Publication Date: 2022-10-18
• Publication Date (W3CDTF): 2022-10-18
• Alternative Title: microRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1
• Degree grantor/type: 鹿児島大学
• Date Granted: 2022-10-18
• Date Granted (W3CDTF): 2022-10-18
• Dissertation Number: 甲総研第673号
• Degree Type: 博士(医学); Doctor of Philosophy in Medical Science
• Text Language Code: eng
• Subject Heading: bladder cancer; cellular senescence; gemcitabine resistance; miR-99a-5p; SMARCD1
• NDC: 490
• 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; 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
• Persistent ID (NDL): info:ndljp/pid/12509577; https://dl.ndl.go.jp/pid/12509577
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 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
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2023-01-30T13:49:37+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10232/00032139
• Data Provider (Database): 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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