Detection of aberrant miRNA expression of malignant lymphoma
| Project/Area Number |
21591191
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Akita University |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | microRNA / NK/T cell lymphoma / 悪性リンパ腫 / マイクロRNA / NK / T細胞リンパ腫 / AKTシグナル / PTEN / SHIP1 |
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| Research Abstract |
MicroRNA (miRNA ; miR) is a class of small regulatory RNA molecules, the aberrant expression of which can lead to the development of cancer. We recently reported that over expression of miR-21 and/or miR-155 leads to activation of the PI3K-AKT pathway in malignant lymphomas expressing CD3^-CD56^+ natural killer (NK) cell antigen. Through expression analysis, we show here that in both NK/T-cell lymphoma lines and samples of primary lymphoma, levels of miR-150 expression are significantly lower than in normal NK cells. To examine its role in lymphomagenesis, we transduced miR-150 into NK/T-cell lymphoma cells, which increased the incidence of apoptosis and reduced cell proliferation. Moreover, the miR-150 transductants appeared senescent and showed lower telomerase activity, resulting in shortened telomeric DNA. We also found that miR-150 directly downregulated expression of DKC1 and AKT2, reduced levels of phosphorylated AKT^<ser473/4>, and increased levels of tumor suppressors such as Bim and p53. Collectively, these results suggest that miR-150 acts as a tumor suppressor, and that its aberrant downregulation induces continuous activation of the PI3K-AKT pathway, leading to telomerase activation and immortalization of cancer cells. These findings provide new insight into the pathogenesis of malignant lymphoma.
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] The role of microRNA-150 as a tumor suppressor in malignant lymphoma.2011
Author(s)
Watanabe A, Tagawa H, Yamashita J, Teshima K, NaraM, Iwamoto K, Kume M, Kameoka Y, Takahashi N, Nakagawa T, Shimizu N, Sawada K
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Journal Title
Leukemia
Volume: 25
Pages: 1324-34
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[Journal Article] CpG-ODN 2006 and human parvovirus B19 genome consensus sequences selectively inhibit growth and development of erythroid progenitor cells2010
Author(s)
Guo YM, Ishii K, Hirokawa M, Tagawa H, Ohyagi H, Michishita Y, Ubukawa K, Yamashita J, Ohteki T, Onai N, Kawakami K, Xiao W, Sawada K
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Journal Title
Blood
Volume: 115
Pages: 4569-79
Related Report
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[Journal Article] Aberrant overexpression of microRNAs activate AKT signaling via downregulation of tumor suppressors in NK-cell lymphoma/leukemia2009
Author(s)
Yamanaka Y, Tagawa H, Takahashi N, Watanabe A, Guo Y-M, Iwamoto K, Yamashita J, Saitoh H, Kameoka Y, Shimizu N, Ichinohasama R, Sawada K
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Journal Title
Blood
Volume: 114
Pages: 3265-74
Related Report
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[Journal Article] Enucleation of human erythroblasts involves non-muscle myosin IIB
Author(s)
Ubukawa K, Guo YM, Takahashi M, Hirokawa M, Michishita Y, Nara M, Tagawa H, Takahashi N, Komatsuda Nunomura W, Takakuwa Y, Sawada K
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Journal Title
Related Report
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