| Project/Area Number |
26670510
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Saeki Norihisa 国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (80466200)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 神経芽腫 / がん遺伝子 / 転写調節因子 / 治療標的分子 / microRNA / マイクロRNA / LMO1 / 創薬標的分子 |
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| Outline of Final Research Achievements |
Overall survival for the high-risk (HR) group of neuroblastoma (NB) patients still remains at 40 to 50%, necessitating the establishment of a curable treatment. LIM domain only 1 (LMO1) gene encoding a transcriptional regulator is an NB-susceptibility gene with a tumor-promoting activity. Previously we conducted chromatin immunoprecipitation and DNA sequencing analyses on NB cell lines and identified 3 protein-coding genes regulated by LMO1. In this study, we extended our analyses to capture microRNA genes directly or indirectly regulated by LMO1. Using microarrays, we conducted a comparative gene expression analysis on an NB cell line SK-N-SH; between the cells with and without LMO1 suppression, and identified 18 microRNAs indirectly down-regulated by LMO1. They included 7 microRNAs of the let-7 family, whose cell proliferation inhibition activity was observed. Target genes of the LMO1-regulated microRNAs and their relevant pathways may be a potential therapeutic target.
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