○種別 (必須): | □ | 学術論文 (審査論文)
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○言語 (必須): | □ | 英語
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○審査 (推奨): |
○カテゴリ (推奨): |
○共著種別 (推奨): |
○学究種別 (推奨): |
○組織 (推奨): |
○著者 (必須): | 1. | 岡崎 潤
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○学籍番号 (推奨): | □ | ****
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| 2. | 棚橋 俊仁
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| 3. | 佐藤 康史 ([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).地域消化器・総合内科学])
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○学籍番号 (推奨): |
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| 4. | 三好 人正
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○学籍番号 (推奨): | □ | ****
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| 5. | 中川 忠彦
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○学籍番号 (推奨): | □ | ****
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| 6. | 木村 哲夫
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| 7. | 宮本 弘志 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.消化器内科学]/[徳島大学.病院.診療科.内科.消化器内科])
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| 8. | 藤野 泰輝
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| 9. | 中村 文香
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○学籍番号 (推奨): | □ | ****
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| 10. | 武原 正典
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| 11. | (英) ma beibei (日) 馬 貝貝 (読) ま べいべい
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○学籍番号 (推奨): | □ | ****
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| 12. | 板東 正浩 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.消化器内科学])
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| 13. | 北村 晋志
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| 14. | 岡本 耕一 ([徳島大学.病院.診療科.内科.消化器内科])
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| 15. | 六車 直樹
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| 16. | 曽我部 正弘 ([徳島大学.キャンパスライフ健康支援センター])
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| 17. | 高山 哲治 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.消化器内科学])
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○題名 (必須): | □ | (英) MicroRNA-296-5p Promotes Cell Invasion and Drug Resistance by Targeting Bcl2-Related Ovarian Killer, Leading to a Poor Prognosis in Pancreatic Cancer. (日)
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○副題 (任意): |
○要約 (任意): | □ | (英) 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). 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. 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. 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. (日)
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○キーワード (推奨): |
○発行所 (推奨): |
○誌名 (必須): | □ | Digestion ([Karger])
(pISSN: 0012-2823, eISSN: 1421-9867)
○ISSN (任意): | □ | 1421-9867
ISSN: 0012-2823
(pISSN: 0012-2823, eISSN: 1421-9867) Title: DigestionTitle(ISO): DigestionPublisher: S. Karger AG (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login])
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○巻 (必須): | □ | 101
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○号 (必須): | □ | 6
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○頁 (必須): | □ | 794 806
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○都市 (任意): |
○年月日 (必須): | □ | 西暦 2020年 11月 初日 (令和 2年 11月 初日)
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○URL (任意): |
○DOI (任意): | □ | 10.1159/000503225 (→Scopusで検索)
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○PMID (任意): | □ | 31563901 (→Scopusで検索)
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○CRID (任意): |
○WOS (任意): |
○Scopus (任意): | □ | 2-s2.0-85072925180
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○備考 (任意): | 1. | (英) Article.ELocationID: 10.1159/000503225 (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 3. | (英) KeywordList.Keyword: Apoptosis (日)
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| 4. | (英) KeywordList.Keyword: Biomarker (日)
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| 5. | (英) KeywordList.Keyword: Epithelial-mesenchymal transition (日)
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| 6. | (英) KeywordList.Keyword: MicroRNA (日)
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| 7. | (英) KeywordList.Keyword: Pancreatic cancer (日)
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