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  1. 医歯学総合研究科
  2. 医歯学総合研究科・博士論文

Molecular Pathogenesis of Colorectal Cancer: Impact of Oncogenic Targets Regulated by Tumor Suppressive miR-139-3p

http://hdl.handle.net/10232/00032559
http://hdl.handle.net/10232/00032559
50452181-63e0-40a1-8503-fd06e1ebffe3
名前 / ファイル ライセンス アクション
Diss_安留_龍太郎_ISK703_2023.pdf Diss_安留_龍太郎_ISK703_2023 (3.0 MB)
Copyright © 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Abstract_安留_龍太郎_4519810338_2023.pdf Abstract_安留_龍太郎_4519810338_2023 (38.2 kB)
Result_YASUDOME_Ryutaro_isk_703.pdf Result_YASUDOME_Ryutaro_isk_703 (130.8 kB)
Comments_YASUDOME_Ryutaro_isk_703.pdf Comments_YASUDOME_Ryutaro_isk_703 (62.4 kB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2023-06-05
タイトル
タイトル Molecular Pathogenesis of Colorectal Cancer: Impact of Oncogenic Targets Regulated by Tumor Suppressive miR-139-3p
別言語のタイトル
その他のタイトル 大腸癌の分子病態 : 癌抑制型マイクロRNA(miR-139-3p)により制御される癌促進型遺伝子の影響
著者 安留, 龍太郎

× 安留, 龍太郎

WEKO 142906

安留, 龍太郎

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著者よみ
姓名 ヤスドメ, リュウタロウ
別言語の著者
姓名 YASUDOME, Ryutaro
言語
言語 eng
キーワード
主題言語 en
主題Scheme Other
主題 microRNA
キーワード
主題言語 en
主題Scheme Other
主題 expression signature
キーワード
主題言語 en
主題Scheme Other
主題 miR-139-3p
キーワード
主題言語 en
主題Scheme Other
主題 tumor suppressor
キーワード
主題言語 en
主題Scheme Other
主題 colorectal cancer
キーワード
主題言語 en
主題Scheme Other
主題 KRT80
キーワード
主題言語 en
主題Scheme Other
主題 HK2
キーワード
主題言語 en
主題Scheme Other
主題 AKT
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(Abstract)
内容記述タイプ Other
内容記述 We recently determined the RNA sequencing-based microRNA (miRNA) expression signature of colorectal cancer (CRC). Analysis of the signature showed that the expression of both strands of pre-miR-139 (miR-139-5p, the guide strand, and miR-139-3p, the passenger strand) was significantly reduced in CRC tissues. Transient transfection assays revealed that expression of miR-139-3p blocked cancer cell malignant transformation (e.g., cell proliferation, migration, and invasion). Notably, expression of miR-139-3p markedly blocked RAC-alpha serine/threonine-protein kinase (AKT) phosphorylation in CRC cells. A combination of in silico database and gene expression analyses of miR-139-3p-transfected cells revealed 29 putative targets regulated by miR-139-3p in CRC cells. RNA immunoprecipitation analysis using an Argonaute2 (AGO2) antibody revealed that KRT80 was efficiently incorporated into the RNA-induced silencing complex. Aberrant expression of Keratin 80 (KRT80) was detected in CRC clinical specimens by immunostaining. A knockdown assay using small interfering RNA (siRNA) targeting KRT80 showed that reducing KRT80 expression suppressed the malignant transformation (cancer cell migration and invasion) of CRC cells. Importantly, inhibiting KRT80 expression reduced AKT phosphorylation in CRC cells. Moreover, hexokinase-2 (HK2) expression was reduced in cells transfected with the KRT80 siRNAs or miR-139-3p. The involvement of miRNA passenger strands (e.g., miR-139-3p) in CRC cells is a new concept in miRNA studies. Our tumor-suppressive miRNA-based approach helps elucidate the molecular pathogenesis of CRC.

Ryutaro Yasudome, Naohiko Seki, Shunichi Asai, Yusuke Goto, Yoshiaki Kita, Yuto Hozaka, Masumi Wada, Kan Tanabe, Tetsuya Idichi, Shinichiro Mori and Takao Ohtsuka
Molecular Pathogenesis of Colorectal Cancer: Impact of Oncogenic Targets Regulated by Tumor Suppressive miR-139-3p
International Journal of Molecular Sciences 2022, 23, 11616
https://doi.org/10.3390/ijms231911616
作成日
日付 2023-05-11
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)
内容記述タイプ Other
内容記述 博士論文全文
ファイル(説明)
内容記述タイプ Other
内容記述 博士論文要旨
ファイル(説明)
内容記述タイプ Other
内容記述 最終試験結果の要旨
ファイル(説明)
内容記述タイプ Other
内容記述 論文審査の要旨
公開者・出版者
出版者 MDPI
公開者・出版者
出版者 鹿児島大学
公開者よみ
公開者よみ カゴシマ ダイガク
公開者別名
公開者別名 Kagoshima University
備考
備考 【指導教員:大塚隆生】
date.appl
【学位申請日】2023-01-04
学位名
学位名 博士(医学)Doctor of Philosophy in Medical Science
学位授与機関
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 鹿児島大学
学位授与年月日
学位授与年月日 2023-05-25
学位授与番号
学位授与番号 甲総研第703号
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