| Project/Area Number |
18K16360
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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 |
Takeda Takashi 大阪大学, 医学部附属病院, 医員 (20781793)
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | エンハンサー / enChIP法 / 三次元ゲノム構造 / 癌幹細胞 / 幹細胞マーカー / エンハンサー領域 |
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| Outline of Final Research Achievements |
To identify the enhancer region of stem cell related genes in colorectal cancer (CRC), we performed enChIP (engineered DNA-binding molecule-mediated chromatin immunoprecipitation) method, which can identify the DNA, RNA, and proteins binding to a specific genomic region. As a result, we identified the enhancer candidate region that binds to the promoter region of KLF5 gene in CRC. KLF5 is a transcription factor belongs to a kruppel-like factor family and the expression is specifically up-regulated in particular human tumors. KLF5 is also known as a cancer stem cell marker for CRC. Next, we generated the deletion mutants of KLF5 enhancer candidate region by CRISPR/Cas9 system and identified the accurate enhancer region at the downstream of KLF5 gene. Moreover, the deletion mutants of KLF5 enhancer region showed the decreased stem cell properties, indicating that KLF5 enhancer region is important for the augmentation of the cancer stemness in CRC.
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| Academic Significance and Societal Importance of the Research Achievements |
癌幹細胞は再発や転移の根源であり、癌幹細胞を標的とした治療法開発のためには、その性質を把握することが必須である。本研究では、enChIP法を用いた解析によって、大腸癌における三次元ゲノム構造を介した幹細胞関連遺伝子の発現制御メカニズムを明らかにすることを目的とした。本研究の結果、大腸癌幹細胞関連遺伝子であるKLF5遺伝子のエンハンサー領域が三次元ゲノム構造を介して遺伝子発現を制御し、幹細胞性を増強させている可能性を明らかとすることができた。この結果は、癌幹細胞を標的とした治療法の開発につながる可能性がある。
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