| Project/Area Number |
18K16860
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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 56050:Otorhinolaryngology-related
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| Research Institution | Tokai University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 選択的スプライシング / 頭頸部癌 / CPSF1 / RNA-Seq / 扁平上皮癌 / RNA-seq |
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| Outline of Final Research Achievements |
We investigated the mechanism of carcinogenesis via ASEs in HNC using RNA sequencing and examined. First, we selected candidate genes from splicing-related genes using TCGA data, and examined the phenotypes of the candidate genes using HNC cell lines. As a result, several genes were selected as candidate genes. Next, after creating overexpression and knockdown cell lines, RNA was extracted, and ASEs induced were identified by RNA-Seq analysis. The results showed that splicing-related gene aberrations induced ASEs of many oncogenes. Abnormalities in splicing-related genes induce ASEs in HNC and may be involved in carcinogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
遺伝子変異以外の発癌機構として遺伝子発現の下流である転写後調節レベルの選択的スプライシングによる発癌機構が明らかになってきている。このスプライシングによる発癌機構が頭頸部癌の発癌に重要な役割を果たしている可能性が十分あると考え今回の研究を行った。本研究によりスプライシング関連遺伝子CPSF1の遺伝子変異は癌関連遺伝子のASEを幅広く誘発し、CPSF1の発現異常は、頭頸部癌においてASEを誘発することにより、発がんに関与している可能性があることが判明した。さらなる研究により頭頸部癌の発癌機構解明、予後向上に貢献できる可能性がある。
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