2023 Fiscal Year Final Research Report
Comprehensive analysis of epigenomic aberrant genes in oral cancer and verification of tumor suppressive effect by epigenomic drugs.
| Project/Area Number |
21K10121
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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 | Health Sciences University of Hokkaido |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
植原 治 北海道医療大学, 歯学部, 講師 (00709248)
吉田 光希 北海道医療大学, 歯学部, 講師 (30453260)
原田 文也 北海道医療大学, 歯学部, 講師 (30824205)
安彦 善裕 北海道医療大学, 歯学部, 教授 (90260819)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 口腔がん / エピゲノム / DNA脱メチル化剤 |
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| Outline of Final Research Achievements |
In this study, we investigated the inhibitory effects of the DNA demethylating agent Zebularine (Zebu) and the histone deacetylase inhibitor Valproic acid (Vpa) on oral tumors. RNA sequencing of the tongue squamous cell carcinoma cell line HSC4 treated with Zebu and Vpa revealed CNTN4 among the top expressed genes. For the tumor suppressor genes p16, p21, RASSF1, NPY, and CNTN4, increased mRNA expression, decreased DNA methylation rates, and reduced HDAC activity were observed. In HSC4-transplanted mice treated with Zebu and Vpa, the tumor size inhibition, increased mRNA expression and decreased DNA methylation rates of tumor suppressor genes were observed. The effects of DNA demethylation and HDAC activity reduction may contribute to the increased mRNA expression of tumor suppressor genes.
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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 |
本研究は、DNA脱メチル化剤Zebularine(Zebu)とヒストン脱アセチル化酵素阻害剤Valproic acid(Vpa)を組み合わせて使用することで口腔腫瘍を抑制することが可能となり、その機序についてエピジェネティクスレベルで解明したものであることから、本研究成果の学術的意義は大きいものと考えられた。本研究成果は、口腔腫瘍に対する新たな治療法開発につながる基礎的データとなり得るものと考えられ、社会的に有益な意義を提供するものと考えられた。
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