{"created":"2023-07-27T06:30:12.350689+00:00","id":15125,"links":{},"metadata":{"_buckets":{"deposit":"e5a74340-2139-4fda-8ad1-ecc45304e47f"},"_deposit":{"created_by":3,"id":"15125","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"15125"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00015125","sets":["4161:3020:3021"]},"author_link":["68978","76362","196","2309","26716","23697","2944"],"item_4_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2017-03-24","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"12","bibliographicPageEnd":"4884","bibliographicPageStart":"4873","bibliographicVolumeNumber":"292","bibliographic_titles":[{"bibliographic_title":"Journal of Biological Chemistry"}]}]},"item_4_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"中野, 正隆"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"深見, 達基"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"中嶋, 美紀 "}],"nameIdentifiers":[{},{},{}]}]},"item_4_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Dihydrofolate reductase (DHFR) plays a key role in folate metabolism and is a target molecule of methotrexate. An increase in the cellular expression level of DHFR is one of the mechanisms of tumor resistance to methotrexate. The present study investigated the possibility that adenosine-to-inosine RNA editing, which causes nucleotide conversion by adenosine deaminase acting on RNA (ADAR) enzymes, might modulate DHFR expression. In human breast adenocarcinoma-derived MCF-7 cells, 26 RNA editing sites were identified in the 3′-UTR of DHFR. Knockdown of ADAR1 decreased the RNA editing levels of DHFR and resulted in a decrease in the DHFR mRNA and protein levels, indicating that ADAR1 up-regulates DHFR expression. Using a computational analysis, miR-25-3p and miR-125a-3p were predicted to bind to the non-edited 3′-UTR of DHFR but not to the edited sequence. The decrease in DHFR expression by the knockdown of ADAR1 was restored by transfection of antisense oligonucleotides for these miRNAs, suggesting that RNA editing mediated up-regulation of DHFR requires the function of these miRNAs. Interestingly, we observed that the knockdown of ADAR1 decreased cell viability and increased the sensitivity of MCF-7 cells to methotrexate. ADAR1 expression levels and the RNA editing levels in the 3′-UTR of DHFR in breast cancer tissues were higher than those in adjacent normal tissues. Collectively, the present study demonstrated that ADAR1 positively regulates the expression of DHFR by editing the miR-25-3p and miR-125a-3p binding sites in the 3′-UTR of DHFR, enhancing cellular proliferation and resistance to methotrexate. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.","subitem_description_type":"Abstract"}]},"item_4_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"Embargo Period 12 months","subitem_description_type":"Other"}]},"item_4_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学ナノ生命科学研究所 / 金沢大学医薬保健研究域薬学系","subitem_description_type":"Other"}]},"item_4_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00015112","subitem_identifier_reg_type":"JaLC"}]},"item_4_publisher_17":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"American Society for Biochemistry and Molecular Biology Inc."}]},"item_4_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1074/jbc.M117.775684","subitem_relation_type_select":"DOI"}}]},"item_4_source_id_11":{"attribute_name":"NCID","attribute_value_mlt":[{"subitem_source_identifier":"AA00251083","subitem_source_identifier_type":"NCID"}]},"item_4_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0021-9258","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Nakano, Masataka"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"Fukami, Tatsuki"}],"nameIdentifiers":[{},{},{},{}]},{"creatorNames":[{"creatorName":"Gotoh, Saki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Nakajima, Miki"}],"nameIdentifiers":[{},{},{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2018-03-25"}],"displaytype":"detail","filename":"PH-PR-NAKANO-M-4873.pdf","filesize":[{"value":"2.3 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"PH-PR-NAKANO-M-4873.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/15125/files/PH-PR-NAKANO-M-4873.pdf"},"version_id":"742599a6-6e70-4582-a931-33dd22b63e3d"}]},"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":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"A-to-I RNA editing up-regulates human dihydrofolate reductase in breast cancer","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"A-to-I RNA editing up-regulates human dihydrofolate reductase in breast cancer"}]},"item_type_id":"4","owner":"3","path":["3021"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-12-05"},"publish_date":"2017-12-05","publish_status":"0","recid":"15125","relation_version_is_last":true,"title":["A-to-I RNA editing up-regulates human dihydrofolate reductase in breast cancer"],"weko_creator_id":"3","weko_shared_id":3},"updated":"2023-07-27T10:12:28.559327+00:00"}