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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/10232/0003255950452181-63e0-40a1-8503-fd06e1ebffe3
名前 / ファイル | ライセンス | アクション |
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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/). |
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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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 |
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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 |
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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 |