2022 Fiscal Year Final Research Report
Involvement of microRNA and DNA repair mechanisms in the acquisition of therapeutic resistance in Ewing's sarcoma.
| Project/Area Number |
20K09414
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
田仲 和宏 大分大学, 医学部, 教授 (10274458)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | Ewing肉腫 |
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| Outline of Final Research Achievements |
We have conducted research with the aim of elucidating the regulatory mechanism by identifying microRNAs (miRNAs) that are involved in the expression of double strand break (DSB) repair factors and investigating the gene expression changes of these repair factors through comprehensive analysis of miRNAs and their target mRNAs showing significant expression changes after knockdown (KD) using EWS-Fli1-specific siRNA. Ewing's sarcoma cells are likely to acquire resistance to radiation and chemotherapy by enhancing the gene expression of DSB repair factors through miRNA derepression. Therefore, we have identified candidates that may be responsible for the development of treatment resistance.
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| Free Research Field |
肉腫
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| Academic Significance and Societal Importance of the Research Achievements |
我々はDNA修復系因子を標的とする複数のmiRNAを同定した。これらのmiRNAは、siRNAによるEWS-Fli1のKDで発現が上昇することから、融合遺伝子によって抑制される一種のtumor suppressive miRNAである可能性が高い。これらのmiRNA作用機構を明らかにし、その発現異常を補正することで、治療抵抗性を生み出すDSB修復因子を減弱させ、治療への感受性を回復できる可能性がある。Ewing肉腫における治療抵抗性のメカニズム解明に加え、新規治療の標的の同定という側面からも本研究の意義は大きいと考えられる。
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