| Project/Area Number |
24791449
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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 |
Digestive surgery
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| Research Institution | Nippon Medical School |
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Principal Investigator |
AKAGI ICHIRO 日本医科大学, 医学部, 助教 (90552662)
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| Co-Investigator(Renkei-kenkyūsha) |
ISHIBASHI Osamu 大阪府立大学, 生命環境学研究科, 准教授 (70293214)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | PI3K / Akt / miR-141 / miR-200 / DDIT4 / PHLPP2 / PIK3CA / PTEN / FOXO-1 |
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| Outline of Final Research Achievements |
We focused on PI3K-AKT pathway and investigated comprehensively mRNA and miRNA expression in normal and tumorous human esophageal squamous cell lines. Using integrated statistical analyses, we identified miR-141, miR-200b, miR-200c, and miR-205 as highly up-regulated onco-miRs in esophageal squamous cell carcinoma (ESCC). According to the computational program TargetScan and our microarray-based comprehensive gene expression analysis, we detected DNA damage-inducible transcript 4 protein (DDIT4) as a target of miR-200b and miR-200c and which was downregulated in ESCC. Also, we detected PH Domain Leucine-Rich Repeat-Containing Protein Phosphatase 2 (PHLPP2) as a target for miR-141 and which was downregulated in ESCC. As expected, the transfection of miR-141 mimic resulted in significant decrease of the expression of PHLPP2 in esophageal epithelial cell line. These results suggest that miR-141 is a negative regulator of PHLPP2 and promotes cell proliferation in ESCC.
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