Therapeutic applications and effects on liver cancer cells by reprogramming related miRNA
Project/Area Number |
24791417
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Digestive surgery
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Research Institution | Osaka University |
Principal Investigator |
KOGA Chikato 大阪大学, 医学部附属病院, 医員 (70597468)
|
Research Collaborator |
NAGANO Hiroaki 大阪大学, 附属病院, 准教授
KOBAYASHI Shogo 大阪大学, 附属病院消化器外科, 助教
|
Project Period (FY) |
2012-04-01 – 2014-03-31
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | 肝細胞癌 / microRNA / ヒストン / リプログラミング / 癌細胞 |
Research Abstract |
Among three miRNAs that were previously presented for miRNA-mediated reprogramming, miR-302 was expressed at low levels in HCC cells. After transfecting three times with miR-302, the cells were incubated in ES medium for 3 weeks, and then characterized. iPSC-like-spheres were obtained after the 3-week incubation. Spheres presented high NANOG and OCT4 expression, low proliferation, high apoptosis, low epithelial-mesenchymal transition marker expression, and sensitization to drugs. Several miRNAs were changed. cMyc was decreased, and methylation was elevated on histone 3 at lysine 4 (H3K4). Differentiated cells expressed markers of each germ layer (GFAP, FABP4, and ALB). AOF2 (also known as LSD1 or KDM1), one of the targets for miR-302, was repressed in iPSC-like-spheres. Silencing of AOF2 resulted in similar features of iPSC-like-spheres, including cMyc down-regulation and H3K4 methylation. In drug-resistant cells, sensitization was achieved through miR-302-mediated reprogramming.
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Report
(3 results)
Research Products
(9 results)