2022 Fiscal Year Final Research Report
p53 pathway and its potential targeted therapeutic approach
| Project/Area Number |
19K07645
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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 50010:Tumor biology-related
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | がん抑制遺伝子 / p53 / 長鎖非コードRNA |
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| Outline of Final Research Achievements |
The development of anti-cancer drugs targeting the p53 pathway has been slow because p53 is a "tumor suppressor gene", although p53 is the most frequently mutated gene in human malignancies. We found that the lncRNA NEAT1 is a direct transcriptional target of p53, and that a long non-coding RNA, lnc53AC, expression affects the translational level and post-translational modifications of p53 and is involved in the reduction of p53 protein expression.
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| Free Research Field |
分子腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
NEAT1は正常型p53遺伝子が存在する場合にのみ腫瘍抑制作用を発揮し，逆に，p53の機能が正常でない場合には，NEAT1ががんの進行を促進する可能性さえあることがわかった．がんにおけるNEAT1の役割を解明する重要な手がかりとなる．
大腸がんにおけるlnc53AC高発現群は，全生存率のみならず，無病生存率，疾患特異的生存率，無増悪生存率においても有意に予後不良であり，p53活性を制御するoncogenic lncRNAであることを明らかにした．lnc53ACは新しい分子標的治療薬の有力候補となる可能性がある．
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