| Project/Area Number |
20K16323
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
Rashad Sherif 東北大学, 医学系研究科, 助教 (00824088)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | tRNA modifications / Glioma / oxidative stress / tRNA cleavage / Stroke / tRNA / CRISPR / Chemotherapy / translation / Cell Stress / Cell stress |
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| Outline of Research at the Start |
tiRNAs are new small non-coding RNA molecules produced via tRNA cleavage by angiogenin cellular stress. tiRNAs were detected in the plasma of patients with malignancies, but their functional role is not yet explored in glioma or other malignancies to date. I hypothesize that targeting tiRNA generation machinery can be valuable as a therapeutic target for glioma. The aim of this work is to study the dynamics and function of tiRNA in glioma cells and their responses to chemotherapy.
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| Outline of Final Research Achievements |
In this work, I was able to identify a non-canonical Angionenin-independent tRNA cleavage pattern that occurs in vitro and in vivo. I was also able to identify the role of tRNA methylation in driving this tRNA cleavage pattern. Further, I identified the role of a tRNA modifying enzyme, Alkbh1, in glioma pathology. Alkbh1 is associated with worse outcomes in glioma patients. Overexpressing Alkbh1 led to induction of glioma stemness, and upregulation of various genes associated with immune functions of glioma and interaction with neurons. Alkbh1 overexpression also led to more resistance to ROS induced senescence and resistance to oxidative stressors. These findings indicate that Alkbh1 is an important target for glioma therapy that should be targeted to improve outcome.
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| Academic Significance and Societal Importance of the Research Achievements |
Understanding the epitranscriptional processes that govern cellular responses to oxidative stress are important for understanding many diseases, including cancer. The results of this work can help design novel therapies to manipulate tRNA modifications and cleavage and imrpove glioma outcome.
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