Functional analysis of miR-375, a candidate of tumor suppressor miRNA in gastric cancer
| Project/Area Number |
22790349
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human pathology
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| Research Institution | Oita University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | マイクロRNA / 胃癌 / miR-375 |
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| Research Abstract |
In this study, we found that miRNA-375(miR-375) was the most downregulated and that its ectopic expression in gastric carcinoma cells markedly reduced cell viability via the caspase-mediated apoptosis pathway. Interestingly, we found that expression of miR-375 inhibited expression of PDK1, which is a direct target of miR-375, followed by suppression of Akt phosphorylation. Further analysis by gene expression microarray revealed that 14-3-3zeta, a potent antiapoptotic gene, was significantly downregulated at both the mRNA and protein levels in cells transfected with miR-375. The activity of a luciferase reporter containing the miR-375 binding sequence at the 3' untranslated region(UTR) of 14-3-3zeta mRNA was repressed by the ectopic expression of miR-375, suggesting that miR-375 targets the 3' UTR of 14-3-3zeta. In addition, knockdown of either PDK1 or 14-3-3zeta in gastric carcinoma cells induced caspase activation, which was also observed in miR-375-transfected cells, suggesting that miR-375 may exert its proapoptotic function, at least in part, through the downregulation of PDK1 and 14-3-3zeta. Taken together, we propose that miR-375 is a candidate tumor suppressor miRNA in gastric carcinoma
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Report
(3 results)
Research Products
(10 results)
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[Journal Article] Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization2011
Author(s)
Kuroda A, Tsukamoto Y, Nguyen LT, Noguchi T, Takeuchi I, Uchida M, Uchida T, Hijiya N, Nakada C, Okimoto T, Kodama M, Murakami K, Matsuura K, Seto M, Ito H, Fujioka T, Moriyama M
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Journal Title
Related Report
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[Journal Article] Overexpression of miR-210, a downstream target of HIF1α, causes centrosome amplification in renal carcinoma cells2011
Author(s)
Nakada C, Tsukamoto Y, Matsuura K, Nguyen TL, Hijiya N, Uchida T, Sato F, Mimata H, Seto M, Moriyama M
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Journal Title
J Pathol
Volume: 224(2)
Pages: 280-8
Related Report
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[Journal Article] MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3zeta2010
Author(s)
Tsukamoto Y, Nakada C, Noguchi T, Tanigawa M, Nguyen LT, Uchida T, Hijiya N, Matsuura K, Fujioka T, Seto M, Moriyama M
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Journal Title
Cancer Res
Volume: 70(6)
Pages: 2339-49
Related Report
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