| Project/Area Number |
18K07941
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KUWANO Yuki 徳島大学, 大学院医歯薬学研究部(医学域), 講師 (00563454)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | RNA / 超保存領域 / RNAプロセシング / 大腸がん / RNAメチル化 / RNA修飾 / RNAスプライシング / 選択的スプライシング |
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| Outline of Final Research Achievements |
Ultraconserved regions (UCRs) are 481 genomic sequences with 100% identity across humans, rats, and mice. Increasing evidence suggests that non-coding RNAs transcribed from UCRs are involved in various diseases, especially cancers. The human transformer 2β gene (TRA2B) encodes a UCR (uc.138) that spans exon 2 and its neighboring introns. Uc.138 is upregulated in colon cancer cell lines, although it is not translated to Tra2β protein because of its nuclear retention. Nevertheless, the clinical significance and biological functions of uc.138 in colon cancer cells remain unclear. In this study, RNA in situ hybridization showed that uc.138 was predominantly overexpressed in the nucleus of colon adenocarcinoma and adenoma. Overexpression of uc.138 in colon cancer cells promoted cell proliferation by changing the expression of G2/M-related cell cycle regulators.Uc.138 plays an oncogenic role in tumor progression and may become a potential biomarker and therapeutic target in colon cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
超保存領域（UCR）はマウス以上の高等生物のみ進化の過程で獲得したゲノム配列であるが、その生理学的意義は不明である。UCRから転写されるRNA群（T-UCR）の発現異常は、がんを含めた高等生物の複雑な細胞恒常性の破綻を判定するRNAバイオマーカーと成りうる。
UCRの多くはタンパク質をコードしておらず、一部のT-UCRはがん悪性化とともに核への蓄積が認められることから、T-UCRの配列特異的なノックダウンは、正規タンパク質の発現に影響を与えず、新しいコンセプトの核酸医療の開発に繋がる可能性がある。
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