{"created":"2023-07-25T08:14:43.303019+00:00","id":15849,"links":{},"metadata":{"_buckets":{"deposit":"7c480f9a-ae1e-4690-afd9-cbbeddbba157"},"_deposit":{"created_by":18,"id":"15849","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"15849"},"status":"published"},"_oai":{"id":"oai:ir.kagoshima-u.ac.jp:00015849","sets":["57:86"]},"author_link":["139421"],"item_5_date_6":{"attribute_name":"作成日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2021-03-10","subitem_date_issued_type":"Collected"}]},"item_5_date_granted_54":{"attribute_name":"学位授与年月日 ","attribute_value_mlt":[{"subitem_dategranted":"2021-03-17"}]},"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":"Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer, and its prognosis is abysmal; only 25% of patients survive one year, and 5% live for five years. MicroRNA(miRNA) signature analysis ofPDACrevealed that both strands of pre-miR-30c (miR-30c-5p, guide strand; miR-30c-2-3p, passenger strand) were significantly downregulated, suggesting they function as tumor-suppressors in PDAC cells. Ectopic expression assays demonstrated that these miRNAs attenuated the aggressiveness of PDAC cells, e.g., cell proliferation, migration, and invasiveness. Through a combination of in silico analyses and gene expression data, we identified 216 genes as putative oncogenic targets of miR-30c-5p and miR-30c-2-3p regulation in PDAC cells. Among these, the expression of 18 genes significantly predicted the 5-year survival rates of PDAC patients (p < 0.01). Importantly, the expression levels of 10 genes (YWHAZ, F3, TMOD3, NFE2L3, ENDOD1, ITGA3, RRAS, PRSS23, TOP2A, and LRRFIP1) were found to be independent prognostic factors for patient survival (p < 0.01). We focused on TOP2A (DNA Topoisomerase II Alpha) and investigated its potential as a therapeutic target for PDAC. The overexpression of TOP2A and its transcriptional activators (SP1 and HMGB2) was detected in PDAC clinical specimens. Moreover, the knockdown of TOP2A enhanced the sensitivity of PDAC cells to anticancer drugs. Our analyses of the PDAC miRNA signature and tumor-suppressive miRNAs provide important insights into the molecular pathogenesis of PDAC.\n\nTakako Tanaka, Reona Okada, Yuto Hozaka, Masumi Wada, Shogo Moriya, Souichi Satake, Tetsuya Idichi, Hiroshi Kurahara, Takao Ohtsuka and Naohiko Seki\nMolecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes\nCancers 2020, 12(10), 2731\nhttps://doi.org/10.3390/cancers12102731","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604号"}]},"item_5_publisher_23":{"attribute_name":"公開者・出版者","attribute_value_mlt":[{"subitem_publisher":"MDPI","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:大塚隆生】"}]},"item_5_text_47":{"attribute_name":"date.appl","attribute_value_mlt":[{"subitem_text_value":"【学位申請日】2021-01-06"}]},"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":"田中, 貴子","creatorNameLang":"ja"},{"creatorName":"タナカ, タカコ","creatorNameLang":"ja-Kana"},{"creatorName":"Tanaka, Takako","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":"2021-10-01"}],"displaytype":"detail","filename":"Diss_田中_貴子_ISK604_2020.pdf","filesize":[{"value":"5.5 MB"}],"format":"application/pdf","licensetype":"license_6","mimetype":"application/pdf","url":{"label":"Diss_田中_貴子_ISK604_2020","objectType":"fulltext","url":"https://ir.kagoshima-u.ac.jp/record/15849/files/Diss_田中_貴子_ISK604_2020.pdf"},"version_id":"652bfb0a-002b-44a6-9d9d-646cff649ff0"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-10-01"}],"displaytype":"detail","filename":"Abstract_田中_貴子_4518810226_2020.pdf","filesize":[{"value":"175.8 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Abstract_田中_貴子_4518810226_2020","objectType":"abstract","url":"https://ir.kagoshima-u.ac.jp/record/15849/files/Abstract_田中_貴子_4518810226_2020.pdf"},"version_id":"a26945e5-fcd3-4ca5-a6c7-ce37badc4bb3"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-04-15"}],"displaytype":"detail","filename":"Result_Tanaka_Takako_isk_604.pdf","filesize":[{"value":"225.5 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Result_Tanaka_Takako_isk_604","objectType":"other","url":"https://ir.kagoshima-u.ac.jp/record/15849/files/Result_Tanaka_Takako_isk_604.pdf"},"version_id":"dd06ae1d-185e-479b-bd75-7587e1505e22"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-04-15"}],"displaytype":"detail","filename":"Comments_Tanaka_Takako_isk_604.pdf","filesize":[{"value":"90.6 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Comments_Tanaka_Takako_isk_604","objectType":"other","url":"https://ir.kagoshima-u.ac.jp/record/15849/files/Comments_Tanaka_Takako_isk_604.pdf"},"version_id":"11a60aa5-32df-4eb7-bebd-00464a67e32d"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"pancreatic ductal adenocarcinoma","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"microRNA","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"tumor-suppressor","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"miR-30c-5p","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"miR-30c-2-3p","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"TOP2A","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":"Molecular pathogenesis of pancreatic ductal adenocarcinoma : impact of miR-30c-5p and miR-30c-2-3p regulation on oncogenic genes","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Molecular pathogenesis of pancreatic ductal adenocarcinoma : impact of miR-30c-5p and miR-30c-2-3p regulation on oncogenic genes","subitem_title_language":"en"},{"subitem_title":"膵癌の分子病因 : 発癌性遺伝子に対するmiR-30c-5pとmiR-30c-2-3pの影響","subitem_title_language":"ja"}]},"item_type_id":"5","owner":"18","path":["86"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-04-15"},"publish_date":"2021-04-15","publish_status":"0","recid":"15849","relation_version_is_last":true,"title":["Molecular pathogenesis of pancreatic ductal adenocarcinoma : impact of miR-30c-5p and miR-30c-2-3p regulation on oncogenic genes"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2024-01-09T01:59:59.892610+00:00"}