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 |
Section | 一般 |
Research Field |
Medical genome science
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Research Institution | Kobe University (2017-2018) Kobe Gakuin University (2016) |
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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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | Splicing、 / Intron retention, / Dystrophin, / Antisense oligo, / Rhabdomyosarcoma / splicing, / intron retention, / dystrophin, / antisense chemistry, / rhabdomyosarcoma, / tumor, / tumor suppressor gene, / Dystrophin / Intron retention / Splicing / AO therapy |
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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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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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Intron-retained transcripts of the spinal muscular atrophy genes, SMN1 and SMN2.2018
Author(s)
Harahap NIF, Niba ETE, Ar Rochmah M, Wijaya YOS, Saito T, Saito K, Awano H, Morioka I, Iijima K, Lai PS, Matsuo M, Nishio H, Shinohara M.
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Journal Title
Brain & Devwlopment
Volume: 40
Issue: 8
Pages: 670-677
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] New, improved version of the mCOP-PCR screening system for detection of spinal muscular atrophy Gene (SMN1) deletion.2017
Author(s)
Shinohara M, Ar Rochmah M, Nakanishi K, Harahap NIF, Niba ETE, Saito T, Saito K, Takeuchi A, Bouike Y, Nishio H
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Journal Title
Kobe J Med Sci
Volume: 63(2)
Related Report
Open Access
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[Journal Article] Genetic screening of spinal muscular atrophy using a real-time modified COP-PCR technique with dried blood-spot DNA2017
Author(s)
Ar Rochmah M, Harahap NIF, Niba ETE, Nakanishi K, Awano H, Morioka I, Iijima K, Saito T, Saito K, Lai PS, Takeshima Y, Takeuchi A, Bouike Y, Okamoto M, Nishio H, Shinohara M
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Journal Title
Brain Dev.
Volume: 39(9)
Issue: 9
Pages: 774-782
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] SMA diagnosis: Detection of SMN1 deletion with real-time mCOP-PCR system using fresh blood DNA2017
Author(s)
Niba ETE, Ar Rochmah M, Harahap NIF, Awano H, Morioka I, Iijima K, Saito T, Saito K, Takeuchi A, Lai PS, Bouike Y, Nishio H, Shinohara M.
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Journal Title
Kobe J Med Sci
Volume: 63(3)
NAID
Related Report
Open Access
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[Journal Article] Gender effects on the clinical phenotype in Japanese patients with spinal muscular atrophy.2017
Author(s)
Ar Rochmah M, Shima A, Harahap NIF, Niba ETE, Morisada N, Yanagisawa S, Saito T, Kaneko K, Saito K, Morioka I, Iijima K, Lai PS, Bouike Y, Nishio H, Shinohara M
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Journal Title
Kobe J Med Sci
Volume: 63(2)
Related Report
Open Access
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[Presentation] Spontaneous development of spindle cell sarcoma in mdx mice2018
Author(s)
: Satoru Takafuji, Emma Niba, Khin Kyae Mon Thwin, Nobuyuki Yamamoto, Hiroyuki Awano, Suguru Uemura, Takeshi Mori, Shoji Fukushima, Kyoko Itoh, Hisahide Nishio, Masafumi Matsuo, Kazumoto Iijima, Noriyuki Nishimura
Organizer
International Society of Pediatric Oncology
Related Report
Int'l Joint Research
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