癌抑制型マイクロRNA(miR-130b-5p)が制御する膵臓癌・機能性ネットワークの探索 : 癌遺伝子EPS8の臨床的重要性

Material type: 博士論文

Author: 福久, はるひ

Publisher: nature

Publication date: -

Material Format: Digital

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Name of awarding university/degree: 鹿児島大学,博士(医学),Doctor of Philosophy in Medical Science

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Note (General)：: 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Our ongoing analyses identifying dysregulated microRNAs (miRNAs) and their controlled target RNAs have shed light on...

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Material Type: 博士論文
Title: 癌抑制型マイクロRNA(miR-130b-5p)が制御する膵臓癌・機能性ネットワークの探索 : 癌遺伝子EPS8の臨床的重要性
Author/Editor: 福久, はるひ
Author Heading: 福久, はるひフクヒサ, ハルヒ
Publication, Distribution, etc.: nature
Alternative Title: Gene regulation by antitumor miR-130b-5p in pancreatic ductal adenocarcinoma : the cinical significance of oncogenic EPS8
Degree grantor/type: 鹿児島大学
Date Granted: 2020-03-25
Dissertation Number: 甲総研第551号
Degree Type: 博士(医学)
Doctor of Philosophy in Medical Science
Text Language Code: eng
Subject Heading: microRNA
passenger strand
miR-130b-5p
pancreatic ductal adenocarcinoma
EPS8
antitumor
Target Audience: 一般
Note (General): 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
Our ongoing analyses identifying dysregulated microRNAs (miRNAs) and their controlled target RNAs have shed light on novel oncogenic pathways in pancreatic ductal adenocarcinoma (PDAC). The PDAC miRNA signature obtained by RNA sequencing showed that both strands of pre-miR-130b (miR-130b-5p, the passenger strand and miR-130b-3p, the guide strand) were significantly downregulated in cancer tissues. Our functional assays revealed that miR-130b-5p significantly blocked the malignant abilities of PDAC cell lines (PANC-1 and SW1990), e.g., cancer cell proliferation, migration and invasion. A total of 103 genes were identified as possible oncogenic targets by miR-130b-5p regulation in PDAC cells based on genome-wide gene expression analysis and in silico database search. Among the possible targets, high expression of 9 genes (EPS8, ZWINT, SMC4, LDHA, GJB2, ZCCHC24, TOP2A, ANLN and ADCY3) predicted a significantly poorer prognosis of PDAC patients (5-year overall survival, p < 0.001). Furthermore, we focused on EPS8 because its expression had the greatest impact on patient prognosis (overall survival, p < 0.0001). Overexpression of EPS8 was detected in PDAC clinical specimens. Knockdown assays with siEPS8 showed that its overexpression enhanced cancer cell proliferation, migration and invasion. Analysis of downstream RNA networks regulated by EPS8 indicated that MET, HMGA2, FERMT1, RARRES3, PTK2, MAD2L1 and FLI1 were closely involved in PDAC pathogenesis. Genes regulated by antitumor miR-130b-5p were closely involved in PDAC molecular pathogenesis. Our approach, discovery of antitumor miRNAs and their target RNAs, will contribute to exploring the causes of this malignant disease. Haruhi Fukuhisa, Naohiko Seki, Tetsuya Idichi, Hiroshi Kurahara, Yasutaka Yamada, Hiroko Toda, Yoshiaki Kita, Yota Kawasaki, Kiyonori Tanoue, Yuko Mataki, Kosei Maemura & Shoji Natsugoe Gene regulation by antitumor miR-130b-5p in pancreatic ductal adenocarcinoma: the clinical significance of oncogenic EPS8 Journal of Human Genetics volume 64, pages521–534 (2019) https://doi.org/10.1038/s10038-019-0584-6
Format (IMT): application/pdf
Source: Diss_福久_はるひ_ISK551_2019 （fulltext）
https://ir.kagoshima-u.ac.jp/record/15181/files/Diss_%E7%A6%8F%E4%B9%85_%E3%81%AF%E3%82%8B%E3%81%B2_ISK551_2019.pdf
Access Restrictions: インターネット公開
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 鹿児島大学 : 鹿児島大学リポジトリ