| Project/Area Number |
16K11228
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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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| Research Field |
Otorhinolaryngology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
三澤 清 浜松医科大学, 医学部附属病院, 講師 (90334979)
遠藤 志織 浜松医科大学, 医学部附属病院, 診療助教 (10625205)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | DNA脱メチル化 / エピゲノムリプログラミング / 頭頸部がん / エピゲノム / リプログラミング / 転写因子 / 頭頸部癌 / 不均一性 / シングルセル解析 |
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| Outline of Final Research Achievements |
DNA demethylation is necessary for the epigenetic reprogramming.The ten eleven translocation protein (TET) might function as a 5-methylcytosine (5mC) oxidase and potentially as a DNA demethylase.TET belongs to a family of three proteins, namely TET1, TET2, and TET3, which catalyze the successive oxidation of 5mC
to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). The 5-hmC profiles in primary tumors may be used to identify patients with positive lymph node metastasis and high tumor stage that are at a higher risk of recurrence. The methylation status of TET3 was independently associated with aggressive tumor behavior and a global effect on DNA methylation status in head and neck cancer.
We conclude that the demethylation of promoter DNA may be a necessary step in the epigenetic reprogramming of head and neck cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
頭頸部癌は予後不良の癌腫の一つである。腫瘍発生のメカニズムは不明な点た多い。今回我々は、DNA脱メチル化が、頭頸部癌発生の重要な機序の一つであると考えた。DNA脱メチル化酵素(TET)は、酸化酵素であり5mCを5hmCへと脱メチル化させる作用を持つ。5hmCは、リンパ節転移、高悪性度頭頸部癌症例で低レベルであった。TET3遺伝子高メチル化は、高悪性度頭頸部癌症例で認められた。さらに癌抑制遺伝子群の高メチル化も認め、悪性度を示す因子であることを解明した。
今回の研究で、エピゲノムリプログラミング調節機構の解明と新たな頭頸部癌の治療の開発の可能性を示すことができた。
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