2022 Fiscal Year Final Research Report
Development of therapeutic methods for drug-resistant oral cancer targeting super-enhancers
| Project/Area Number |
20H03883
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
伊豫田 学 千葉大学, 大学院医学研究院, 助教 (40431746)
中嶋 大 千葉大学, 大学院医学研究院, 助教 (50431747)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | スーパーエンハンサー / 抗癌剤耐性 / ChIP-seq |
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| Outline of Final Research Achievements |
We applied chromatin immunoprecipitation sequencing (ChIP-Seq) to profile super-enhancers (SE) using two independent cetuximab-resistant OSCC cell lines. In total, 64 chromosomal loci by histone H3 lysine 27 acetylation (H3K27ac) ChIP-Seq were identified as common SE in cetuximab-resistant OSCC cells. In addition, a total of 131 genes were located in SE regions, and 34 genes were upregulated in OSCC tissues by TCGA-OSCC analysis. Moreover, highly expression of four genes (C9orf89, CENPA, PISD, and TRAF2) were predicted as a poorer prognosis factors for OSCC patients according to log-rank tests. Increased expression of the four genes frequently co-occurred in data of TCGA-OSCC analyses. The four genes' high and low expression groups showed significant differences in prognosis. Analysis of these genes could contribute to an improved understanding of cetuximab resistance in OSCC patients.
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| Free Research Field |
口腔癌における分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究での抗癌剤耐性SEの同定を契機に, エピジェネティックな発現制御機構を利用した新規治療法・薬剤を開発することが見込まれ, 真に有効な新しい口腔癌耐性克服への治療応用にむけて大いに期待できるものである. これは, 個々の耐性関連機能ではなく, 系統的に複数の機能を制御する共通エンハンサーを利用するという点できわめてユニークな治療法になるものと言える. また, 担癌患者の長期社会復帰などを実現させる可能性もあり, その社会的意義も大きいと考えている.
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