Project/Area Number |
26670815
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
Allocation Type | Multi-year Fund |
Research Field |
Pathobiological dentistry/Dental radiology
|
Research Institution | Okayama University |
Principal Investigator |
KOZAKI Ken-ichi 岡山大学, 大学院医歯薬学総合研究科, 教授 (50270715)
|
Co-Investigator(Kenkyū-buntansha) |
SOGAWA Norio 松本歯科大学, 歯学部, 教授 (30236153)
SOGAWA Chiharu 岡山大学, 大学院医歯薬学総合研究科, 講師 (10253022)
|
Project Period (FY) |
2014-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 発現制御 / 遺伝子 / 癌 / 発生・分化 / 移植・再生医療 |
Outline of Final Research Achievements |
We established a novel gene promoter activity detection (gPAD) system and utilized it in a cell-based drug screening, in which promoter sequences of marker genes were connected with fluorescent reporter genes and inserted in stable cell clones. Concretely, we established a gPAD system with a promoter sequence of VIM gene that encodes mesenchymal marker vimentin in order to evaluate alteration of epithelial-mesenchymal transition (EMT) program in cancer cells and then performed functional screening using the cell-based reporter system. We established such VIM gPAD system within MKN1 colon cancer cells, performed screening from 328 species of miRNAs, and then identified a novel EMT-inducing microRNA miR-544a. miR-544a was shown to promote EMT through targeting CDH1 gene, encoding an epithelial marker E-cadherin, and targeting AXIN2 gene, encoding a Wnt signaling inhibitory factor, and thus to activate Wnt and TGFβ signaling pathways (Yanaka Y et al., 2015, Carcinogenesis). As above, an example and usefulness of gPAD system in drug screening were shown.
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