2022 Fiscal Year Final Research Report
Molecular mechanism underlying quiescence acquisition in glioma stem cells
| Project/Area Number |
19K09454
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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 56010:Neurosurgery-related
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
野崎 和彦 滋賀医科大学, 医学部, 客員教授 (90252452)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | グリオーマ幹細胞 / quiescence |
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| Outline of Final Research Achievements |
Glioblastoma multiforme is a highly heterogeneous tumor. Resistance to standard therapies is frequent, suggesting that a small subpopulation of glioma stem-like cells (GSCs) within the tumor causes tumor recurrence. It can be distinguished from the tumor cells through the epigenetic regulatory program and disruption in epigenetic processes governs molecular alteration leading to malignant transformation. Here, we demonstrated that the histone H2B E3 ubiquitin ligase RNF20 is necessary for GSCs maintenance and tumor progression. RNF20 downregulation sustained the GSC quiescence pool at a low-proliferation rate, where it possesses long-term self-renewal and higher tumorigenic potential. Besides, RNF20 knockdown cells are more resistant to Temozolomide and reduce apoptosis. The transition to a proliferative state depended upon RNF20 expression patterns, thereby rendering GSCs dependent on RNF20 to maintain their growth and transcriptional processes.
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| Free Research Field |
脳神経外科
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| Academic Significance and Societal Importance of the Research Achievements |
抗がん剤や放射線照射は増殖グリオーマ細胞を死滅させるが、分裂しないために生き残ったグリオーマ幹細胞は再び分裂を開始して大量のグリオーマ細胞を供給すると考えられている。したがって、根本的治療を目指した治療法の開発には、グリオーマ幹細胞のquiescenceをいかに制御するかが重要課題である。本研究はこの問いの解明と重要因子のメカニズム解明を行なった。その結果、エピゲノム因子RNF20が未分化性や細胞周期の調節に寄与し、グリオーマの増殖や浸潤などの悪性度を規定するquiescenceのゲートキーパーである可能性が示唆され、今後のエピゲノム分子を標的とする治療法発展に貢献できた。
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