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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
http://hdl.handle.net/10232/00031761
http://hdl.handle.net/10232/000317615f560a40-8428-4cb7-956b-e524742af709
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Diss_岡村_俊介_ISK608_2021 (2.7 MB)
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Abstract_岡村_俊介_4517810099_2020 (89.9 kB)
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Result_Okamura_Shunsuke_608 (811.2 kB)
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Comments_Okamura_Shunsuke_608 (444.7 kB)
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| 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 | |||||
| タイトル言語 | en | |||||
| タイトル | ||||||
| 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 | |||||
| タイトル言語 | ja | |||||
| 著者 |
岡村, 俊介
× 岡村, 俊介 |
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| 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 | ||||||
| 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. 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 |
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| 内容記述言語 | en | |||||
| 作成日 | ||||||
| 日付 | 2021-05-11 | |||||
| 日付タイプ | Collected | |||||
| 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 | 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 | |||||
| 公開者・出版者 | ||||||
| 出版者 | BMC | |||||
| 出版者言語 | en | |||||
| 公開者・出版者 | ||||||
| 出版者 | 鹿児島大学 | |||||
| 出版者言語 | ja | |||||
| 公開者・出版者 | ||||||
| 出版者 | カゴシマ ダイガク | |||||
| 出版者言語 | ja-Kana | |||||
| 備考 | ||||||
| 備考 | 【指導教員:榎田英樹】 | |||||
| date.appl | ||||||
| appl | 【学位申請日】2021-02-03 | |||||
| 学位名 | ||||||
| 学位名の言語 | ja | |||||
| 学位名 | 博士(医学) | |||||
| 学位名 | ||||||
| 学位名の言語 | en | |||||
| 学位名 | Doctor of Philosophy in Medical Science | |||||
| 学位授与機関名 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 17701 | |||||
| 学位授与機関名の言語 | ja | |||||
| 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 | |||||
