Regulation of novel molecular target ADAM32 in hepatoblastoma and its application to precision medicine

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17554
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Hiroshima University
• Principal Investigator: Fukazawa Takahiro 広島大学, 自然科学研究支援開発センター, 研究員 (80734285)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ADAM32 / 低酸素 / m6Aメチル化 / IGF2BP2 / Harmine

Outline of Final Research Achievements

Treatment results for hepatoblastoma have improved, but there are still some intractable cases, and late effects after treatment are also a big problem. We have previously shown that ADAM32 is specifically highly expressed in hepatoblastoma cells and plays a role as an oncogene, suggesting its potential as a molecular target. In this study, we analyzed the regulation mechanism of ADAM32 by focusing on hypoxia, which is the microenvironment of solid tumors. It was revealed that the upstream molecule IGFP2BP2 plays an important role in ADAM32 mRNA expression. In addition, we found Harmine as a molecule that regulates ADAM32 from database analysis, and showed that it has an anticancer effect on hepatoblastoma.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

肝芽腫に対してより治療効果が高く副作用の少ない分子標的治療法開発が望まれているが未だ開発されていない。肝芽腫における新規分子標的候補ADAM32に対する制御分子としてIGF2BP2を見出した。また、肝芽腫に対して制がん作用を持つ化合物としてHarmineを見出した。これらADAM32制御を可能とする分子、化合物を発見し、肝芽腫制御の新たな可能性を示した本研究は、肝芽腫における新規治療法開発に貢献すると考えられる。