2018 Fiscal Year Final Research Report
Dystrophin intron retention analysis to identify new targets for Antisense Oligonucleotide mediated RNA modulation in Rhabdomyosarcoma
| Project/Area Number |
16K07216
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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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| Research Field |
Medical genome science
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| Research Institution | Kobe University (2017-2018)
Kobe Gakuin University (2016) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
松尾 雅文 神戸学院大学, 総合リハビリテーション学部, 特命教授 (10157266)
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| Research Collaborator |
AWANO HIROYUKI
NISHIMURA NORIYUKI
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | Splicing、 / Intron retention, / Dystrophin, / Antisense oligo, / Rhabdomyosarcoma |
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| Outline of Final Research Achievements |
Dystrophin is regarded as a potential tumor suppressor gene because it was shown to be mutated in a variety of rhabdomyosarcoma and DMD patients sometimes develop some kind of tumors. Therefore, this project was intended to understand the significance of dystrophin as a tumor suppressor in rhabdomyosarcoma.
In this project, the applicants showed that dystrophin intron retention was an important factor of rhabdomyosarcoma formation. They next, designed an antisense oligonucleotide to target the removal of this retained intron. Abolishment of the retained intron was successful. In addition, they showed that abolishing intron retention, increased dystrophin production of a carboxyl-terminal dystrophin isoform. Moreover, the cell proliferation of the rhabdomyosarcoma reduced drastically when intron retention was abolished.
They equally demonstrated the cell specificity, sensitivity and specie specificity of the antisense oligonucleotide. This is antisense could be potential drug for RMS
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| Free Research Field |
Molecular Genetics
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| Academic Significance and Societal Importance of the Research Achievements |
This project will be the first of its kind to use DMD Intron retention (IR) analysis to search for new therapeutic targets in Rhabdomyosarcoma (RMS. It will advance the scientific knowledge of DMD genetic impact on RMS formation, IR as a novel mechanism of RMS formation and Antisense therapy in RMS.
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