Seeking a novel therapy for hereditary breast cancer by modulating alternative splicing
| Project/Area Number |
15K10050
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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 |
General surgery
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| Research Institution | Fukuoka University (2016-2017)
Kyoto University (2015) |
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Principal Investigator |
Ohe Kenji 福岡大学, 薬学部, 准教授 (30419527)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | スプライシング / 遺伝性乳癌 |
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| Outline of Final Research Achievements |
Hereditary breast cancer caused by the BRCA1 mutation 5382insC is due to a one base pair insertion in exon 20 and results in a frame shift. In order to correct this, we tried various ways to skip exon 20, eventually which corrects the frameshift.We tried small splice modifying compounds,antisense RNA, modified U1 snRNA, and modified U7 snRMA, but all ended up in a failure. However, when we evaluated BRCA1 protein (C term Ab)by Western blot, we found TG003 increased the corrected in-frame BRCA1 protein accompanying decreased cell viability of HCC1937 cells which harbor the BRCA1 5382insC mutation endogenously.Exon skipping may have been induced in other exons besides exon 20 by TG003, which we are still persuing.
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] CHCHD2 mutations in autosomal dominant late-onset Parkinson’s disease: a genome-wide linkage and sequencing study.2015
Author(s)
Funayama M, Ohe K, Amo T, Furuya N, Yamaguchi J, Saiki S, Yuanzhe L, Ogaki K, Ando M, Yoshinon H, Tomiyama H, Nishioka K, Hasegawa K, Saiki H, Satake W, Mogushi K, Sasaki R, Kokubo Y, Kuzuhara S, Toda T, Mizuno Y, Uchiyama Y, Ohno K, Hattori N.
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Journal Title
Lancet Neurol
Volume: 14
Issue: 3
Pages: 274-282
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Rectifier of aberrant mRNA splicing recovers tRNA modification in familial dysautonomia.2015
Author(s)
Yoshida M, Kataoka N, Miyauchi K, Ohe K, Iida K, Yoshida S, Nojima T, Okuno Y, Onogi H, Usui T, Takeuchi A, Hosoya T, Suzuki T, Hagiwara M.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 112（9）
Issue: 9
Pages: 2764-2769
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Identification of RNA-binding proteins responsible for aberrant tissue-specific splicing of the IKBKAP gene in Familial dysautonomia2015
Author(s)
Kenji Ohe, Mayumi Yoshida, Akiko Nakano-Kobayashi, Kensuke Ninomiya, Maki Sakuma, Tomomi Usui, Takayuki Nojima, Naoyuki Kataoka, Masatoshi Hagiwara
Organizer
EUKARYOTIC mRNA PROCESSING meeting 2015, Cold Spring Harbor Laboratory
Place of Presentation
New York, USA
Year and Date
2015-08-18
Related Report
Int'l Joint Research
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