Mechanism of neuroblastoma development by MYCN-PRC2 mediated epigenomic aberrations

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15208
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Nagoya University
• Principal Investigator: Tsubota Shoma 名古屋大学, 医学系研究科, 助教 (10801657)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 神経芽腫 / MYCN / PRC2 / EZH2

Outline of Final Research Achievements

Neuroblastoma is a childhood cancer, and is caused by the well-known oncogene, MYCN. The applicant previously reported that EZH2, an epigenomic regulator, is important for MYCN-induced neuroblastoma development, that MYCN binds to EZH2, and that inhibition EZH2 function can prevent neuroblastoma growth. In this study, we investigated whether the binding of MYCN to EZH2 is essential for the development of neuroblastoma. Unfortunately, we could not reproduce the previous report that a part of MYCN is required for the binding of EZH2 in the first place, so we did not achieve our goal within the study period.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

MYCNの過剰発現は神経芽腫を引き起こす原因の1つであるが、その構造的特性から特異的な阻害剤の開発は困難である。そのため、MYCNによるがん化の詳細な機構を解明することで、MYCNそのものではなくMYCNにより引き起こされる異常を標的とした治療薬の開発が可能となる。本研究はその基盤となるMYCNとEZH2の結合が、MYCNによる神経芽腫の発生に必須であるということを調査するものであり、これが達成されればこの結合阻害が新たな治療標的になりうる。