2018 Fiscal Year Final Research Report
Altered RNA editing and malignant progression in oral squamous carcinoma.
| Project/Area Number |
15K11265
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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 |
Surgical dentistry
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| Research Institution | Health Sciences University of Hokkaido |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
磯貝 恵美子 東北大学, 農学研究科, 教授 (80113570)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Keywords | エピジェネティク / ADAR1 / AZIN1 / FLNB / 口腔扁平上皮癌 |
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| Outline of Final Research Achievements |
Recently, adenosine (A)-to-inosine (I) RNA editing, as it is catalyzed by adenosine deaminases on acting on RNA (ADAR) has been shown to be a potential epigenetic event in human cancers. Here we investigated that role of RNA editing enzyme ADARs and altered RNA editing in oral squamous carcinoma (OSCC) malignant progression. Among the three ADAR enzymes expressed in human cells, only ADAR1was expressed in OSCC cells. We used to modulate the expression of ADAR1 by overexpressing, or silencing ADAR1 reinstating a specific altered edited transcript. As a result of the overexpression of ADAR1in OSCC cells, led to the increased editing frequencies of antizyme inhibitor 1 (AZIN1) and filamin B (FLNB) transcripts. Consistently, silencing ADAR1 by shRNA targeting ADAR1 gene in OSCC cells resulted in the reduced editing level of AZIN1 and FLNB.
These results suggest that the upregulation of ADAR1 in OSCC contributes to the gene specific altered editing pattern.
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| Free Research Field |
口腔外科学
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| Academic Significance and Societal Importance of the Research Achievements |
A-to-I編集を担うADARsが、ヒトの癌における潜在的なエピジェネティクな変化に関与していることが示されている。そこで、我々は悪性化進展におけるRNA編集酵素ADARとADARによるRNA編集異常の役割について検討した。その結果、口腔扁平上皮癌ではADAR1の過剰発現によってAZIN1とFLNBに編集異常を起こし、悪性化進展を促進していることが示された。これらの結果から、ADARの異常発現が RNA 編集異常の頻度を高め悪性化進展に関与することを示した。
本研究によって、RNA編集異常を標的とした診断法や治療法の開発に向けての基盤研究が確立できると考えられる。
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