{"created":"2023-07-25T08:13:34.504456+00:00","id":14454,"links":{},"metadata":{"_buckets":{"deposit":"cfdf9a42-0d6c-4133-9d92-9c69cdc3bab3"},"_deposit":{"created_by":18,"id":"14454","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"14454"},"status":"published"},"_oai":{"id":"oai:ir.kagoshima-u.ac.jp:00014454","sets":["57:86"]},"author_link":["132193"],"item_5_biblio_info_5":{"attribute_name":"収録雑誌名","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2018-05-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"33","bibliographicPageEnd":"23017","bibliographicPageStart":"23003","bibliographicVolumeNumber":"9","bibliographic_titles":[{"bibliographic_title":"Oncotarget","bibliographic_titleLang":"en"}]}]},"item_5_date_granted_54":{"attribute_name":"学位授与年月日 ","attribute_value_mlt":[{"subitem_dategranted":"2018-11-20"}]},"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":"Sunitinib is a standard molecular-targeted drug used as a first-line treatment for metastatic clear cell renal cell carcinoma (ccRCC); however, resistance to sunitinib has become a major problem in medical practice. Recently, bromodomain containing 4 (BRD4), a member of the bromodomain family proteins, was identified as a promising therapeutic target, and its inhibitor JQ1 has been shown to have inhibitory effects in  various human cancers. However, the anti-cancer effects of JQ1 in ccRCC, particularly sunitinib-resistant ccRCC, are still unclear. Here, we aimed to elucidate the anti-cancer effects of JQ1 and the mechanisms underlying BRD4 inhibition in sunitinib-sensitive and -resistant ccRCCs. Analysis of The Cancer Genome Atlas (TCGA) ccRCC cohort showed that patients with high BRD4 expression had shorter overall survival than those with low expression. JQ1 treatment significantly inhibited tumor growth of sunitinib-sensitive and -resistant ccRCC cells in part through MYC regulation. Based on RNA sequencing analyses of ccRCC cells treated with JQ1 to elucidate the mechanisms other than MYC regulation, we identified several oncogenes that may be potential therapeutic targets or prognostic markers; patients with high expression of SCG5, SPOCD1, RGS19, and ARHGAP22 had poorer overall survival than those with low expression in TCGA ccRCC cohort. Chromatin immunoprecipitation assays revealed that these oncogenes may be promising BRD4 targets, particularly in sunitinib-resistant ccRCC cells. These results identified SCG5, SPOCD1, RGS19, and ARHGAP22 as potential prognostic markers and showed that BRD4 inhibition may have applications as a potential therapeutic approach in sunitinib-sensitive and -resistant ccRCC.","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486号"}]},"item_5_publisher_23":{"attribute_name":"公開者・出版者","attribute_value_mlt":[{"subitem_publisher":"鹿児島大学","subitem_publisher_language":"ja"},{"subitem_publisher":"Oncotarget","subitem_publisher_language":"en"},{"subitem_publisher":"カゴシマ ダイガク","subitem_publisher_language":"ja-Kana"}]},"item_5_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.18632/oncotarget.25190","subitem_relation_type_select":"DOI"}}]},"item_5_relation_13":{"attribute_name":"情報源","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"Oncotarget"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://www.oncotarget.com/","subitem_relation_type_select":"URI"}}]},"item_5_subject_15":{"attribute_name":"NDC","attribute_value_mlt":[{"subitem_subject":"493","subitem_subject_scheme":"NDC"}]},"item_5_text_44":{"attribute_name":"備考","attribute_value_mlt":[{"subitem_text_value":"【指導教員:中川昌之】"}]},"item_5_text_47":{"attribute_name":"date.appl","attribute_value_mlt":[{"subitem_text_value":"【学位申請日】2018/7/4"}]},"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":"坂口, 大","creatorNameLang":"ja"},{"creatorName":"サカグチ, タカシ","creatorNameLang":"ja-Kana"},{"creatorName":"Sakaguchi, Takashi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"132193","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2018-12-04"}],"displaytype":"detail","filename":"Diss_坂口大_ISK486_2018.pdf","filesize":[{"value":"12.2 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MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Result_Sakaguchi_Takashi_isk_486_2018","objectType":"other","url":"https://ir.kagoshima-u.ac.jp/record/14454/files/Result_Sakaguchi_Takashi_isk_486_2018.pdf"},"version_id":"05e7ea5e-64cf-4ed8-af49-1323bb069509"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2018-12-04"}],"displaytype":"detail","filename":"Comments_Sakaguchi_Takashi_isk_486_2018.pdf","filesize":[{"value":"476.9 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Comments_Sakaguchi_Takashi_isk_486_2018","objectType":"other","url":"https://ir.kagoshima-u.ac.jp/record/14454/files/Comments_Sakaguchi_Takashi_isk_486_2018.pdf"},"version_id":"2a496dd8-ba75-40a7-aedb-515c0b7f0485"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"bromodomain","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"BRD4","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"JQ1","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"sunitinib resistance","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"renal cell carcinoma","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":"Bromodomain protein BRD4 inhibitor JQ1 regulates potential prognostic molecules in advanced renal cell carcinoma","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Bromodomain protein BRD4 inhibitor JQ1 regulates potential prognostic molecules in advanced renal cell carcinoma","subitem_title_language":"en"},{"subitem_title":"進行腎細胞癌においてブロモドメイン蛋白BRD4阻害剤JQ1は複数の有望な予後予測因子を制御する","subitem_title_language":"ja"}]},"item_type_id":"5","owner":"18","path":["86"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2018-12-04"},"publish_date":"2018-12-04","publish_status":"0","recid":"14454","relation_version_is_last":true,"title":["Bromodomain protein BRD4 inhibitor JQ1 regulates potential prognostic molecules in advanced renal cell carcinoma"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2024-01-09T01:48:45.735178+00:00"}