Identification of the super-enhancers that regulate radioresistance of oral cancer and development of new therapeutic agents

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K19222
• 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, 医学部附属病院, 医員 (40833554)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: ATAC-seq / スーパーエンハンサー / 口腔癌放射線耐性 / 口腔癌放射線感受性 / DAVID-GO解析 / モチーフ解析

Outline of Final Research Achievements

By radiosensitivity assays of nine oral squamous cell carcinoma (OSCC) derived cell lines, we determined the radioresistant OSCC cell (HSC-3) and radiosensitive OSCC cell (KOSC-2). To investigate changes of chromatin accessibility in the radioresistant/sensitivity cells, we performed the dynamic genetic analyses, such as the Transposase-Accessible Chromatin Sequencing (ATAC-seq), DAVID-GO gene analysis, and motif analysis for detection of driver genes/transcription factors about radiosensitivity in OSCCs. As a result, adenylate cyclase 2 (ADCY2) expression was significantly up-regulated and RUNX2, a transcriptional factor, was concentrated in the opened region in HSC-3 cells after 8 Gy irradiation. RUNX2 has been reported to form super-enhancer (SE) in other types of cancer, suggesting that ADCY2 and RUNX may be critical factors for SE formation.

Free Research Field

医歯薬学 歯学・外科系歯学

Academic Significance and Societal Importance of the Research Achievements

口腔癌に関しては、スーパーエンハンサーの制御などエピゲノムの変化から導いた放射耐性に関する報告はない。放射線耐性に関与するゲノムレベルの変化からの研究は、新規医学・医療技術を用いた研究であり、全ゲノム的で系統的な遺伝子・機能制御は、大きな発想の転換である。放射線治療耐性の克服は、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。