Development of a novel therapeutic strategy against medulloblastoma targeting Myc by DIF-1

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16634
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Saga University
• Principal Investigator: Ito Hiroshi 佐賀大学, 医学部, 助教 (50795375)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Medulloblastoma / MYC / DIF-1

Outline of Final Research Achievements

Medullooblastoma (MB) is a representative pediatric brain tumor. Group 3/4 medulloblastoma with MYC amplification have a poor prognosis. DIF-1 had been reported its anti-tumor effect in various cancer. We revealed DIF-1 reduced expression of Myc by transcriptional repression, caused apoptosis and downregulated cell growth in MB cell lines. This downregulation of cell growth is more remarkable in MYC amplified MB cell lines.
However, MYC knock down by siRNA did not downregulated cell growth in MB cell lines. It suggested that downregulation of cell growth in MB cells may not be involved in transcriptional repression of MYC.
We concluded that DIF-1 may be a therapeutic option, but further studies are necessary about its mechanism.

Free Research Field

脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

最も予後不良なGroup3/4髄芽腫に対する標的治療はない。予後不良な因子としてMYC増幅が報告されているがMYCを直接標的とした治療もない。本研究では、DIF-1が髄芽腫細胞のMYC転写を抑制し、かつMYC増幅細胞の細胞増殖を抑制することを示した。ただし、DIF-1による細胞増殖抑制は単純なMyc発現抑制によるものではないことが明らかとなった。
本研究の結果、DIF-1が髄芽腫治療候補になりうる可能性を示したことやDIF-1にMYC自身の転写を抑制する効果があることが示されたため他癌種においてもMYCを標的とする新たな治療候補としての有効性も提示できたことに意義がある。