Reactivation of Tumor-suppressor MicroRNAs in Cancer Cells by Epigenome Editing
| Project/Area Number |
20K07604
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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 50010:Tumor biology-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Gailhouste Luc 国立研究開発法人理化学研究所, 開拓研究本部, 研究員 (40848537)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Granted (Fiscal Year 2021)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | microRNA / Epigenome editing / Tumor-suppressor / DNA methylation / dCas9-Tet1 / MicroRNAs / epigenome editing / tumor-suppressor / cancer |
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| Outline of Research at the Start |
1. Apr. to Dec. 2020: in silico analysis and design of the gRNAs. Challenge of targeted epigenome editing and demethylation of the candidate tumor-suppressor miRNAs in cancer cells.
2. Jan. to June 2021: assessment of the recovery of tumor-suppressor activities mediated by the reactivation of the miRNAs.
3. July 2021 to June 2022: tumor growth models (in vivo).
4. July 2022 to March 2023: compilation of the data, analyses, manuscript writing, submission, and potential revision
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| Outline of Annual Research Achievements |
The objective of this project was to develop a reliable system for targeted demethylation and reactivation of specific cancer-related microRNAs (miRNAs). By adapting the CRISPR-Cas9 system and establishing an innovative editing technology, we have been able to accurately manipulate the epigenome of tumor-suppressor miRNAs for functional analyses and potential therapeutic applications. Thus far, the following aims have been achieved:
1. Targeted demethylation of the tumor-suppressor miR-122 using the dCas9-TET1 epigenome editing system
2. Identification of miR-122 targets using miRNA epigenome editing
3. miR-122 editing negatively impacts hepatic cancer cell growth through SLC2A3 targeting
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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
This work is currently in progress as expected. Tumor-suppressor miRNA epigenome editing using animal experimental models will be achieved this year.
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| Strategy for Future Research Activity |
We are currently applying targeted demethylation of miRNAs to other types of tumor cells, especially pancreatic ductal adenocarcinoma cells. Importantly, reactivation of tumor-suppressor miRNAs other than miR-122 is in progress to demonstrate the versatility of our miRNA epigenome editing system. Further functional analyses will help to clarify interactions between the edited miRNAs and their potential targets. Last, mouse tumor growth models will be used to validate the therapeutic potential of miRNA epigenome editing.
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Report
(2 results)
Research Products
(5 results)
