2021 Fiscal Year Research-status 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 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 | Glioma / Chemotherapy / tRNA / Cell Stress |
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| Outline of Annual Research Achievements |
1) To understand the links between tRNA and Glioma, ALKBH1 overexpression was performed in glioma cell line. Alkbh1 is a tRNA demethylase that enhances tRNA cleavage. Alkbh1 overexpression enhanced glioma invasion, stemness, and resistance to oxidative stress. Alkbh1 achieved its activity via tRNA demethylation, protein translation repression, and translational shifts. Furthermore, Alkbh1 protected glioma cells against ferroptosis. 2) m7G modification was analyzed in glioma cells. Loss of m7G via WDR4 knockdown led to inhibition of proliferation and invasion and induction of stemness. 3) Conducted a study using human surgical glioblastoma samples to analyze tRNA derived small RNA landscape using small RNA sequencing. Data analysis is in progress. 4) Conducted a study on the mechanisms of tiRNA generation during oxidative stress. Identified stress-specific signatures that impact tRNA cleavage in different forms of stress such as mitochondrial stress and endoplasmic reticulum stress. Identified impact of tRNA cleavage on protein translation using ribosome profiling and bioinformatics analysis.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Several tRNA methylation modifications were discovered to impact glioma pathophysiology. Currently, shRNA and CRISPR knockout based approached are being used to probe the function of these modifications in glioma and their impact on tRNA cleavage and translation.
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| Strategy for Future Research Activity |
Work will be continued on m1A modifications their responsible enzyme, Alkbh1, as well as on m7G modifications and WDR4 enzyme in glioma. Animal experiments are planned to understand the impact of tRNA methylation on glioma microenvironment and immune responses.
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