| Project/Area Number |
18K15099
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Tokai University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 膵臓 / 膵管癌 / Necl-4 / miRNA / 細胞接着因子 / miRNA mimic / 細胞接着 / microRNA |
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| Outline of Final Research Achievements |
In this study, We examined the expression and function of miRNAs that regulate the expression of Necl-4. We performed a comprehensive microarray search and identified one miRNA that was significantly up-regulated in Necl-4-knockdown cells. Furthermore, in pancreatic ductal carcinonma cells transfected with miRNA mimic and miRNA inhibitor, we confirmed that the miRNA that was upregulated by the microarray repressed the expression of Necl-4. In addition, TP53、SMAD4, which are major tumor suppressor genes of pancreatic ductal carcinoma, were down-regulated in Necl-4-knockdown cells, while the expression of one miRNA was up-regulated.
These results suggest that down-regulation of Necl-4 is associated with down-regulation of pancreatic ductal carcinoma-related tumor suppressor genes and up-regulation of miRNAs that regulate them.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、細胞接着因子の一つであるNecl-4の発現を制御するmiRNAを膵管癌細胞で同定した。更に、Necl-4-knockdown細胞で発現亢進していたmiRNAがNecl-4の発現を抑制することを明らかにした。また、Necl-4抑制細胞およびNecl-4関連miRNAが膵癌関連癌抑制遺伝子の発現変動に関わることが示唆された。本研究の成果は、Necl-4関連miRNAを対象とした独自的・創造的な新規バイオマーカーや治療法の開発への発 展が期待され、学術的・社会的に意義があるものと考えられる。
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