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  1. 医歯学総合研究科
  2. 医歯学総合研究科・博士論文

microRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1

http://hdl.handle.net/10232/00032139
http://hdl.handle.net/10232/00032139
ead38c77-0fd5-4f85-a9e7-467b51ed0fb6
名前 / ファイル ライセンス アクション
Diss_玉井_元規_ISK673_2022.pdf Diss_玉井_元規_ISK673_2022 (2.7 MB)
Abstract_玉井_元規_4518810244_2022.pdf Abstract_玉井_元規_4518810244_2022 (166.6 kB)
Result_TAMAI_Motoki_isk_673.pdf Result_TAMAI_Motoki_isk_673 (134.8 kB)
Comments_TAMAI_Motoki_isk_673.pdf Comments_TAMAI_Motoki_isk_673 (52.3 kB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2022-10-27
タイトル
タイトル microRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1
別言語のタイトル
その他のタイトル 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 玉井, 元規

× 玉井, 元規

WEKO 141338

玉井, 元規

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著者よみ
姓名 タマイ, モトキ
別言語の著者
姓名 TAMAI, Motoki
言語
言語 eng
キーワード
主題言語 en
主題Scheme Other
主題 bladder cancer
キーワード
主題言語 en
主題Scheme Other
主題 cellular senescence
キーワード
主題言語 en
主題Scheme Other
主題 gemcitabine resistance
キーワード
主題言語 en
主題Scheme Other
主題 miR-99a-5p
キーワード
主題言語 en
主題Scheme Other
主題 SMARCD1
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_db06
資源タイプ doctoral thesis
アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
要約(Abstract)
内容記述タイプ Other
内容記述 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 Yoshino
microRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1
Molecular Oncology 16(6), 1329-1346 (2022)
https://doi.org/10.1002/1878-0261.13192
作成日
日付 2022-10-07
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
NDC
主題Scheme NDC
主題 490
ファイル(説明)
内容記述タイプ Other
内容記述 博士論文全文
ファイル(説明)
内容記述タイプ Other
内容記述 博士論文要旨
ファイル(説明)
内容記述タイプ Other
内容記述 最終試験結果の要旨
ファイル(説明)
内容記述タイプ Other
内容記述 論文審査の要旨
公開者・出版者
出版者 Federation of European Biochemical Societies / John Wiley & Sons Ltd
公開者・出版者
出版者 鹿児島大学
公開者よみ
公開者よみ カゴシマ ダイガク
公開者別名
公開者別名 Kagoshima University
備考
備考 【指導教員:榎田英樹】
date.appl
【学位申請日】2022-04-06
学位名
学位名 博士(医学)Doctor of Philosophy in Medical Science
学位授与機関
学位授与機関識別子Scheme kakenhi
学位授与機関識別子 17701
学位授与機関名 鹿児島大学
学位授与年月日
学位授与年月日 2022-10-18
学位授与番号
学位授与番号 甲総研第673号
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