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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

EHHADH contributes to cisplatin resistance through regulation by tumor-suppressive microRNAs in bladder cancer

http://hdl.handle.net/10232/00031761
http://hdl.handle.net/10232/00031761
5f560a40-8428-4cb7-956b-e524742af709
名前 / ファイル ライセンス アクション
Diss_岡村_俊介_ISK608_2021.pdf Diss_岡村_俊介_ISK608_2021 (2.7 MB)
Abstract_岡村_俊介_4517810099_2020.pdf Abstract_岡村_俊介_4517810099_2020 (89.9 kB)
Result_Okamura_Shunsuke_608.pdf Result_Okamura_Shunsuke_608 (811.2 kB)
Comments_Okamura_Shunsuke_608.pdf Comments_Okamura_Shunsuke_608 (444.7 kB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2021-05-26
タイトル
タイトル EHHADH contributes to cisplatin resistance through regulation by tumor-suppressive microRNAs in bladder cancer
別言語のタイトル
その他のタイトル シスプラチン耐性膀胱癌における、癌抑制型microRNAを介した、EHHADHの役割
著者 岡村, 俊介

× 岡村, 俊介

WEKO 139485

岡村, 俊介

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著者よみ
姓名 オカムラ, シュンスケ
別言語の著者
姓名 OKAMURA, Shunsuke
言語
言語 eng
キーワード
主題言語 en
主題Scheme Other
主題 Cisplatin resistance
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 EHHADH
キーワード
主題言語 en
主題Scheme Other
主題 miR-486-5p
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 Background: Cisplatin-based chemotherapy is recommended as the primary treatment for advanced bladder cancer (BC) with unresectable or metastatic disease. However, the benefits are limited due to the acquisition of drug resistance. The mechanisms of resistance remain unclear. Although there are some reports that some molecules are associated with cisplatin resistance in advanced BC, those reports have not been fully investigated. Therefore, we undertook a new search for cisplatin resistance-related genes targeted by tumor suppressive microRNAs as well as genes that were downregulated in cisplatin-resistant BC cells and clinical BC tissues.
Methods: First, we established cisplatin-resistant BOY and T24 BC cell lines (CDDP-R-BOY, CDDP-R-T24). Then, Next Generation Sequence analysis was performed with parental and cisplatin-resistant cell lines to search for the microRNAs responsible for cisplatin resistance. We conducted gain-of-function analysis of microRNAs and their effects on cisplatin resistance, and we searched target genes comprehensively using Next Generation mRNA sequences.
Results: A total of 28 microRNAs were significantly downregulated in both CDDP-R-BOY and CDDP-R-T24. Among them, miR-486-5p, a tumor suppressor miRNA, was negatively correlated with the TNM classification of clinical BC samples in The Cancer Genome Atlas (TCGA) database. Transfection of miRNA-486-5p significantly inhibited cancer cell proliferation, migration, and invasion, and also improved the cells’ resistance to cisplatin. Among the genes targeted by miRNA-486-5p, we focused on enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase (EHHADH), which is involved in the degradation of fatty acids. EHHADH was directly regulated by miRNA-486-5p as determined by a dual-luciferase reporter assay. Loss-of-function study using EHHADH si-RNA showed significant inhibitions of cell proliferation, migration, invasion and the recovery of cisplatin sensitivity.
Conclusion: Identification of EHHADH as a target of miRNA-486-5p provides novel insights into the potential mechanisms of cisplatin resistance in BC.
要約(Abstract)
内容記述タイプ Other
内容記述 Shunsuke Okamura, Hirofumi Yoshino, Kazuki Kuroshima, Masafumi Tsuruda, Yoichi Osako, Takashi Sakaguchi, Masaya Yonemori, Yasutoshi Yamada, Shuichi Tatarano, Masayuki Nakagawa and Hideki Enokida
EHHADH contributes to cisplatin resistance through regulation by tumor-suppressive microRNAs in bladder cancer
BMC Cancer (2021) 21:48
https://doi.org/10.1186/s12885-020-07717-0
作成日
日付 2021-05-11
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 BMC
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】2021-02-03
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 2021-05-17
学位授与番号
学位授与番号 甲総研第608号
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