| Project/Area Number |
18K07915
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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 | Nagoya City University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
松浦 健太郎 名古屋市立大学, 医薬学総合研究院(医学), 講師 (30580576)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 肝繊維化 / 発がん / TLL1 / 肝発がん / メタロプロテアーゼ / 肝線維化 / TGFβシグナル |
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| Outline of Final Research Achievements |
We found that short transcript variants of the TLL1 gene was increased in patients who have the risk allele of a polymorphism in the TLL1 gene which is associated with hepatocellular carcinoma development after cure of hepatitis C. TLL1 is known to cleave one of oncogenic proteins, ANGPTL2 suggesting that TLL1 act as an tumor suppressor protein. Protease assay revealed that c-terminal-truncated TLL1 encoded by the short transcript variants do not have enzymatic activity, suggesting that the increase of non-functional TLL1 may be insufficient for interfere oncogenic function of ANGPTL2 in the patients with TLL1 risk allele.
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| Academic Significance and Societal Importance of the Research Achievements |
C型肝炎は強力な抗ウイルス薬の登場により完全治癒が可能となったが、その後の肝発がんリスクは依然として高い。発がんリスク上昇に関与する TLL1 遺伝子多型を持つ患者の肝臓内では短いTLL1 mRNAの比率が上昇しているが、本研究ではそのmRNAがコードするTLL1は機能欠損型であり、発がんプロモータ分子ANGPTL2の分解活性を持たないことを示した。TLL1の発がん抑制メカニズムを詳細に解析を進めることにより、C型肝炎治癒後の肝発がんを抑制可能な分子ターゲットを同定できることが期待される。
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