| Item type |
文献 / Documents(1) |
| 公開日 |
2020-01-20 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
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資源タイプ |
doctoral thesis |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1159/000503225 |
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関連名称 |
10.1159/000503225 |
| 出版タイプ |
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出版タイプ |
NA |
|
出版タイプResource |
http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| タイトル |
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|
タイトル |
MicroRNA-296-5p Promotes Cell Invasion and Drug Resistance by Targeting Bcl2-Related Ovarian Killer, Leading to a Poor Prognosis in Pancreatic Cancer |
| タイトル別表記 |
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その他のタイトル |
マイクロRNA296-5pはBcl2-Related Ovarian Killer遺伝子を介して細胞浸潤と薬剤耐性を促進し、膵癌の不良予後に寄与する |
| タイトル別表記 |
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その他のタイトル |
miRNA-296-5p and BOK in Pancreatic Cancer |
| 著者 |
岡崎, 潤
棚橋, 俊仁
佐藤, 康史
三好, 人正
中川, 忠彦
木村, 哲夫
宮本, 弘志
藤野, 泰輝
中村, 文香
武原, 正典
マ, ベイベイ
板東, 正浩
北村, 晋志
岡本, 耕一
六車, 直樹
曽我部, 正弘
高山, 哲治
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| 抄録 |
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内容記述 |
Background/Aims: Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive invasion, early metastasis, and resistance to chemotherapy, leading to a poor prognosis. To clarify the molecular mechanism of these malignant characteristics, we performed a genome-wide microRNA (miRNA) array analysis utilizing micro-cancer tissues from patients with unresectable PDAC (stage IV), obtained by endoscopic ultrasound-fine needle aspiration (EUS-FNA). Methods: The expression profiles of 2,042 miRNAs were determined using micro-cancer tissues from 13 patients with unresectable PDAC obtained by EUS-FNA. The relationship between individual miRNA levels and overall survival (OS) was analyzed. Possible target genes for miRNAs were bioinformatically analyzed using the online database miRDB. Pancreatic cancer cell lines PANC-1, MIA PaCa-2, and PK-8 were transfected with miRNA mimic or small interfering RNA, and cell invasion, epithelial-mesenchymal transition (EMT), and apoptosis markers were examined. miRNA and mRNA expressions were examined by quantitative polymerase chain reaction. Results: Of 2,042 miRNAs, the 10 that exhibited the lowest correlation coefficient (p ≤ 0.005) between miRNA expression level and OS among the patients were identified. The miRDB and expression analysis in cancer cell lines for the 10 miRNAs identified miR-296-5p and miR-1207-5p as biomarkers predictive of shorter survival (p < 0.0005). Bioinformative target gene analysis and transfection experiments with miRNA mimics showed that Bcl2-related ovarian killer (BOK), a pro-apoptotic gene, is a target for miR296-5p in pancreatic cancer cells; transfection of miR-296-5p mimic into PANC-1, MIA PaCa-2, and PK-8 cells resulted in significant suppression of BOK mRNA and protein expression. These transfectants showed significantly higher invasion capability compared with control cells, and knock down of BOK in pancreatic cancer cells similarly enhanced invasion capability. Transfectants of miR-296-5p mimic also exhibited aberrant expression of EMT markers, including vimentin and N-cadherin. Moreover, these transfectants showed a significantly lower apoptosis rate in response to 5-fluorouracil and gemcitabine with a decrease of BOK expression, suggesting a role of miR-296-5p in drug resistance. Conclusion: These results suggest that miR-296-5p is a useful biomarker for a poor prognosis in patients with PDAC, and that the miR-296-5p/BOK signaling axis plays an important role in cell invasion, drug resistance, and EMT in PDACs. |
| キーワード |
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主題 |
Apoptosis |
| キーワード |
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主題 |
Biomarker |
| キーワード |
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|
主題 |
Epithelial-mesenchymal transition |
| キーワード |
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主題 |
MicroRNA |
| キーワード |
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主題 |
Pancreatic cancer |
| 書誌情報 |
en : Digestion
巻 101,
号 6,
p. 794-806,
発行日 2019-09-27
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
00122823 |
| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
14219867 |
| 収録物ID |
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収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA00628636 |
| 収録物ID |
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収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA12781324 |
| 出版者 |
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出版者 |
Karger |
| 備考 |
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|
値 |
内容要旨・審査要旨・論文本文の公開
本論文は，著者Jun Okazakiの学位論文として提出され，学位審査・授与の対象となっている。
学位授与者所属 : 徳島大学大学院医科学教育部（医学専攻） |
| 権利情報 |
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権利情報 |
© 2019 S. Karger AG, Basel |
| EID |
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識別子 |
360161 |
| 言語 |
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言語 |
eng |
| 報告番号 |
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学位授与番号 |
甲第3341号 |
| 学位記番号 |
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値 |
甲医第1433号 |
| 学位授与年月日 |
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学位授与年月日 |
2019-12-26 |
| 学位名 |
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学位名 |
博士（医学） |
| 学位授与機関 |
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学位授与機関名 |
徳島大学 |
k3341_abstract_review.pdf (166 KB)
