{"created":"2023-07-25T08:15:02.021380+00:00","id":16254,"links":{},"metadata":{"_buckets":{"deposit":"c1f40d40-af61-4f5c-84e8-288591cd22a4"},"_deposit":{"created_by":18,"id":"16254","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"16254"},"status":"published"},"_oai":{"id":"oai:ir.kagoshima-u.ac.jp:00016254","sets":["57:86"]},"author_link":["141338"],"item_5_date_6":{"attribute_name":"作成日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2022-10-07","subitem_date_issued_type":"Collected"}]},"item_5_date_granted_54":{"attribute_name":"学位授与年月日 ","attribute_value_mlt":[{"subitem_dategranted":"2022-10-18"}]},"item_5_degree_grantor_53":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"鹿児島大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"17701","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_5_degree_name_42":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)","subitem_degreename_language":"ja"},{"subitem_degreename":"Doctor of Philosophy in Medical Science","subitem_degreename_language":"en"}]},"item_5_description_17":{"attribute_name":"ファイル（説明）","attribute_value_mlt":[{"subitem_description":"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","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_5_description_4":{"attribute_name":"要約(Abstract)","attribute_value_mlt":[{"subitem_description":"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.\n\nMotoki 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\nmicroRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1\nMolecular Oncology 16(6), 1329-1346 (2022)\nhttps://doi.org/10.1002/1878-0261.13192","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_5_dissertation_number_55":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲総研第673号"}]},"item_5_publisher_23":{"attribute_name":"公開者・出版者","attribute_value_mlt":[{"subitem_publisher":"Federation of European Biochemical Societies / John Wiley & Sons Ltd","subitem_publisher_language":"en"},{"subitem_publisher":"鹿児島大学","subitem_publisher_language":"ja"},{"subitem_publisher":"カゴシマ ダイガク","subitem_publisher_language":"ja-Kana"}]},"item_5_subject_15":{"attribute_name":"NDC","attribute_value_mlt":[{"subitem_subject":"490","subitem_subject_scheme":"NDC"}]},"item_5_text_44":{"attribute_name":"備考","attribute_value_mlt":[{"subitem_text_value":"【指導教員:榎田英樹】"}]},"item_5_text_47":{"attribute_name":"date.appl","attribute_value_mlt":[{"subitem_text_value":"【学位申請日】2022-04-06"}]},"item_5_version_type_14":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"玉井, 元規","creatorNameLang":"ja"},{"creatorName":"タマイ, モトキ","creatorNameLang":"ja-Kana"},{"creatorName":"Tamai, Motoki","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-11-08"}],"displaytype":"detail","filename":"Diss_玉井_元規_ISK673_2022.pdf","filesize":[{"value":"2.7 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Diss_玉井_元規_ISK673_2022","objectType":"fulltext","url":"https://ir.kagoshima-u.ac.jp/record/16254/files/Diss_玉井_元規_ISK673_2022.pdf"},"version_id":"38c78316-efdc-4a44-8610-12e27e660215"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-10-27"}],"displaytype":"detail","filename":"Abstract_玉井_元規_4518810244_2022.pdf","filesize":[{"value":"166.6 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Abstract_玉井_元規_4518810244_2022","objectType":"abstract","url":"https://ir.kagoshima-u.ac.jp/record/16254/files/Abstract_玉井_元規_4518810244_2022.pdf"},"version_id":"5d0941a0-ce03-44da-ac51-7de728def9ea"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-10-28"}],"displaytype":"detail","filename":"Result_TAMAI_Motoki_isk_673.pdf","filesize":[{"value":"134.8 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Result_TAMAI_Motoki_isk_673","objectType":"other","url":"https://ir.kagoshima-u.ac.jp/record/16254/files/Result_TAMAI_Motoki_isk_673.pdf"},"version_id":"d9ccd747-f5e7-4f76-80b5-a923eb43c0f0"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-10-28"}],"displaytype":"detail","filename":"Comments_TAMAI_Motoki_isk_673.pdf","filesize":[{"value":"52.3 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Comments_TAMAI_Motoki_isk_673","objectType":"other","url":"https://ir.kagoshima-u.ac.jp/record/16254/files/Comments_TAMAI_Motoki_isk_673.pdf"},"version_id":"fd08ccd3-6447-4733-96f2-ce2209e58f1a"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"bladder cancer","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"cellular senescence","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"gemcitabine resistance","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"miR-99a-5p","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"SMARCD1","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"microRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"microRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1","subitem_title_language":"en"},{"subitem_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","subitem_title_language":"ja"}]},"item_type_id":"5","owner":"18","path":["86"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2022-10-27"},"publish_date":"2022-10-27","publish_status":"0","recid":"16254","relation_version_is_last":true,"title":["microRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2024-01-09T02:08:05.306496+00:00"}