Identification of radiation resistance factor in oral cancer by chromatin accessibility analysis and development of novel treatment

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K17081
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Chiba University
• Principal Investigator: Saitoh Tomoaki 千葉大学, 大学院医学研究院, 助教 (40833554)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: クロマチンアクセシビリティ / ATAC-seq / 口腔癌放射線耐性 / オープンクロマチン / ヘテロクロマチン

Outline of Final Research Achievements

We evaluated chromatin accessibility in radioresistant (HSC-3) and radiosensitive (KOSC-2) cells using ATAC-seq. We found 1273 peaks (open chromatin regions) related to 8 Gy irradiation in HSC-3, among which 235 genes located around the chromatin open peaks were identified by ChIPpeakAnno analysis. Subsequently, 12 genes were selected as signal transduction-related genes by Gene Ontology analysis, and RT-qPCR confirmed 12 genes' expression. Among these genes, adenylate cyclase 2 (ADCY2) was significantly upregulated after irradiation in HSC-3 but not KOSC-2 cells. To further evaluate ADCY2 function in radioresistant cells, we performed ADCY2 knockdown by transfection of siADCY2. Cell viability after irradiation was significantly decreased in siADCY2-transfected cells compared with that in control cells. These results suggested that ADCY2 expression was related to the open chromatin region in radioresistant OSCC cells and therapeutic efficacy when used in combination with radiotherapy.

Free Research Field

口腔癌における分子生物学

Academic Significance and Societal Importance of the Research Achievements

口腔癌に関しては，クロマチンアクセシビリティに注目した治療法(抗癌剤・放射線治療)
の報告はない．さらに，本研究は個々の耐性関連機能ではなく，エピジェネティックな制御機構を同定・利用するという点が大きな発想の転換であり、まさに、新規医学・医療技術の開拓を目指した研究である．担癌患者の長期社会復帰などを実現させる可能性があり，社会的意義も大きい．