2020 Fiscal Year Final Research Report
Functional analysis and therapeutic development targeting tRNA methylthiolation in oral squamous cell carcinoma
| Project/Area Number |
19K19204
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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 57060:Surgical dentistry-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | tRNA修飾 / 口腔扁平上皮癌 / SAS / 質量分析 / 抗癌剤耐性 |
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| Outline of Final Research Achievements |
The purpose of this study was to elucidate the effect of methylthiolation (ms2 modification) of mitochondrial tRNA (mt-tRNA) in oral squamous cell carcinoma (OSCC). Analysis using clinical specimens from OSCC patients revealed that ms2 modification was significantly increased in the tumor area compared to the surrounding normal tissue. In addition, when the expression of CDK5RAP1, which is ms2 modifying enzyme, was suppressed in the OSCC cell line SAS, the tumor growth ability decreased. Furthermore, it was found that the ms2 modification was significantly increased in the anticancer drug-resistant cell line as compared with the parent strain. From the above, it was suggested that ms2 modification of mt-tRNA may be involved in the malignancy of OSCC, especially anticancer drug resistance.
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| Free Research Field |
歯科口腔外科学分野
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| Academic Significance and Societal Importance of the Research Achievements |
口腔癌は世界的にみても主要な悪性腫瘍の1つでありその80%以上をOSCC が占めている。近年の診断・治療法の 進歩にも関わらず、5年生存率に大きな改善はみられていない。その原因として、高転移能、治療抵抗性など腫 瘍制御の障壁となる悪性形質をもつ腫瘍細胞が存在していることが挙げられる。tRNA修飾は、迅速かつ正確なタ ンパク質翻訳に寄与していることが示唆されており、近年様々な疾患との関連性が示唆されている。しかしなが ら、tRNA修飾とOSCCの発生・進展との関わりについては未解明なままであり、新たな知見を得ることは現在まで 大きな改善を認めていない治療成績の向上に寄与することが期待される。
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