| Project/Area Number |
18K09798
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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 57060:Surgical dentistry-related
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| Research Institution | Showa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 千洋 昭和大学, 歯学部, 助教 (20783062)
山田 篤 昭和大学, 歯学部, 講師 (50407558)
代田 達夫 昭和大学, 歯学部, 教授 (60235760)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | TPD52ファミリー / 扁平上皮癌 / ｍRNA安定性 / 転写後遺伝子発現調節 / TIA-1 / Hypoxia / オートファジー / 口腔癌 / 翻訳後修飾 / アポトーシス / Squamous cell cartinoma / Oral cncer / TPD52 / HIF-1 |
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| Outline of Final Research Achievements |
In the present study, the following findings were revealed;
(1) TPD52 gene and protein were increased in human oral squamous cell carcinoma (OSCC) cells exposed to hypoxia. (2) This enhancing effect was not dependent on an increase in gene transcription activity or on hypoxia-inducible factor (HIF), but on a post-transcriptional regulation by increased mRNA stability. (3) TPD52 was involved in autophagy, and thereby, increased cell viability of OSCC cells in hypoxia. (4) In the in vivo experiment, TPD52 knockdown showed a synergistic effect with HIF inhibitor, and significantly suppressed the growth and invasion of transplanted OSCC cells.
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| Academic Significance and Societal Importance of the Research Achievements |
口腔扁平上皮癌細胞でTPD52のmRNA、および、タンパクは低酸素刺激で誘導されるが、その作用は転写活性の上昇によるものではなく、もっぱらmRNA安定性の上昇に起因し、この作用はHIFシグナル経路に非依存的であることが明らかとなった。また、TPD52の低酸素下での発現亢進は癌細胞の細胞死抵抗性獲得に関与することが示された。本研究結果によって、TPD52遺伝子は口腔扁平上皮癌における新たな分子標的となりうる可能性が示された。
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