| Project/Area Number |
17K16241
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | Chiba University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Hedgehog経路 / microRNA / 線維芽細胞 / マイクロアレイ / hedgehog signal / map3k1 / Gorlin症候群 / PTCH1 / 髄芽腫 |
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| Outline of Final Research Achievements |
Gorlin syndrome (GS) is a congenital disorder with morphologic anomalies and tumorigenicity, caused by constitutive hyperactivity of hedgehog signaling (HS). While SMO antagonists have been effectively used in the clinical treatment of HS-related cancer, these treatments have severe adverse reactions. To explore a novel therapeutic target for controlling hyper-activated HS, we profiled microRNAs in GS fibroblasts.
We analyzed dermal fibroblasts using microarray comparative genomic hybridization to screen human microRNAs in GS fibroblasts, and identified 35 down- or upregulated microRNAs. Among them, the decrease of hsa-miR-196a-5p and the increase of the target gene, MAP3K1, exhibit significant difference in GS fibroblasts.Additionally, HS induction with exogenous components decreased miR-196a-5p expression and increased map3k1 expression, and map3k1 knock-down induced decreased in cell proliferation. Decreased hsa-miR-196a-5p in GS may contribute to the cell proliferation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究を通して、Gorlin症候群（GS）患者における細胞内microRNAの発現パターンを明らかにし、Hedgehog経路がmicroRNA発現量の変化を介して、細胞増殖に関与している可能性が示唆された。GSの新規治療とHedgehog経路活性のバイオマーカーの探索に有用な知見を得ることができた。本研究で得られた知見は乳癌、髄芽腫、膵癌などのHedgehog経路亢進が関与する固形腫瘍の治療にも応用できる可能性がある。また、他疾患における経路阻害療法へも応用可能な研究手法と考える。このように、本研究は他の増殖経路が関与する先天奇形症候群や固形腫瘍の経路阻害療法への研究の広がりが期待される。
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