2022 Fiscal Year Final Research Report
Studying the dynamics of a novel small RNA (tiRNA) generation in glioma; possible new therapy
| 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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| Keywords | tRNA modifications / Glioma / oxidative stress / tRNA cleavage / Stroke |
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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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| Free Research Field |
Molecular Neurobiology
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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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