| Project/Area Number |
18K16310
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Osaka University |
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Principal Investigator |
Yamada Moyuru 大阪大学, 医学部附属病院, 医員 (00781717)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | circular RNA / 治療抵抗性 / シスプラチン / 食道扁平上皮癌 / Circular RNA / non-coding RNA / 薬剤感受性 / 薬剤耐性 / 次世代シークエンス / 網羅的解析 / non-cording RNA / 核酸医薬 / non coding RNA / 治療抵抗性メカニズムの解明 |
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| Outline of Final Research Achievements |
The prognosis of Esophageal squamous cell carcinoma (ESCC) is poor, underlying mechanisms causing therapy resistance being unknown. Circular RNAs (circRNAs) is a type of non-coding RNAs with closed loop structure. Recently it has been reported that circRNAs have function to modulate the expression of genes. Here, we analyzed the expression profile of human circRNAs in ESCC cells and Cisplatin-resistant cells in order to detect the circRNAs concerning with therapy resistance.
Altogether,19085 circRNAs were identified and 87 were significantly upregulated in TE11R. In qPCR targeting top 10 upregulated circRNAs, CircX was upregulated in Cisplatin resistant TE8 cells as well as in TE11R. In vitro, chemosensitivity assay demonstrated that silence of CircX by siRNA increased Cisplatin-sensitivity in TE11. CircX was identified as upregulated target in Cisplatin-resistant cells and supposed to be concerned with the chemosensitivity in ESCC.
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| Academic Significance and Societal Importance of the Research Achievements |
食道扁平上皮癌における治療抵抗性に関わるcircular RNAの候補として同定された。さらなる検証によりcicXが治療抵抗性のメカニズムがあきらかになれば、circXの配列を鋳型に人工合成した環状RNAを用いた治療抵抗性改善薬の開発を目指したい。また、CircXは食道癌組織でも発現が見られ、治療効果や予後を予測するバイオマーカーとしての可能性についても検討の余地がある。
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