2013 Fiscal Year Final Research Report
Therapeutic application of miRNAs converting malignant propeties to non-malignant level
| Project/Area Number |
23659285
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied pharmacology
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| Research Institution | Tottori University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Keywords | miRNA / 癌 / 幹細胞 / 脱メチル化 |
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| Research Abstract |
To identify the factors inducting stemness by miR-520d-5p, we investigated the effects of lentivirally inducing miR-520d expression in 293FT and HLF cells in vitro. Subsequently, we evaluated tumor formation in a xenograft model.
Transformed HLF cells were Oct4 and Nanog positive within 24 h, showed p53 upregulation and hTERT downregulation, and mostly lost their migration abilities. After lentiviral infection, the cells were intraperitoneally injected into mice, resulting in benign teratomas (6%), the absence of tumors (87%) or differentiation into benign liver tissues (7%) at the injection site after 1 month. We are the first to demonstrate the loss of malignant properties in cancer cells in vivo through the expression of a single microRNA (miRNA). This miRNA successfully converted 293FT and hepatoma cells to hiPSC-like cells. The regulation of malignancy by miR-520d appears to be through the conversion of cancer cells to normal stem cells, maintaining p53
upregulation.
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