Analysis of epigenetic regulation of androgen responsive miRNAs in prostate cancer
| Project/Area Number |
16K18411
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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 |
Tumor biology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
Misawa Aya 日本医科大学, 医学部, 講師 (20598453)
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | lncRNA / 転移 / エピジェネティクス / ncRNA / 骨転移 / 前立腺癌 / 石灰化 / ALPL / HOTAIR / 前立腺がん / TNSAP / miRNA / AR / TNAP |
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| Outline of Final Research Achievements |
HOTAIR is a lncRNA that plays critical role in gene regulation and chromatin dynamics through epigenetic mechanisms. In this work we studied the physiological role of HOTAIR during the process of mineralization using osteoblastic osteosarcoma cells focusing in ALPL Tissue Non-Specific Alkaline Phosphatase), a pivotal gene that controls bone formation. HOTAIR knockdown resulted in upregulation of ALPL, increase of alkaline phosphatase (ALP) activity and enhance d mineralization in osteoblastic SaOS-2 cells cultured in mineralizing medium. Luciferase assays using reporter vector s containing ALPL promoter showed that HOTAIR repression increases ALPL promoter activity. Furthermore, HOTAIR knockdown increased histone H3K4 methylation levels at ALPL promoter region, suggesting that ALPL repression by HOTAIR is regulated by epigenetic mechanisms. This work supports that physiological bone formation is epigenetically regulated by a lncRNA.
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| Academic Significance and Societal Importance of the Research Achievements |
骨の石灰化において中心的な役割を果たすALPL は転移性前立腺がんの増殖に関与していることが報告されている。従って、HOTAIR が ALPL を制御することによって骨の石灰化のみならず、前立腺がんの骨転移にも関与している可能性がある。実際、骨転移した前立腺がんより樹立された VCaP 細胞株は ALPL を発現しており、石灰化することを確認した。前立腺がん細胞は転移巣である骨に到達すると骨特有の性質を示すことが示唆され、本研究は前立腺癌及び骨に転移する他の癌の骨転移のメカニズムに関して新たな手掛かりを与える研究となった。
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Report
(4 results)
Research Products
(7 results)
