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Detection of aberrant miRNA expression of malignant lymphoma

Research Project

Project/Area Number 21591191
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionAkita University

Principal Investigator

TAGWAWA Hiroyuki  秋田大学, 大学院・医学系研究科, 講師 (30373492)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
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)
KeywordsmicroRNA / 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
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.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (10 results)

All 2011 2010 2009 Other

All Journal Article (8 results) (of which Peer Reviewed: 3 results) Presentation (2 results)

  • [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
    • Journal Title

      Leukemia

      Volume: 25 Pages: 1324-34

    • Related Report
      2011 Final Research Report
  • [Journal Article] Aberrant expression of microRNA and its role in malignant lymphoma2011

    • Author(s)
      Tagawa H
    • Journal Title

      Rinsho Ketsueki

      Volume: 52 Pages: 263-71

    • NAID

      10029424846

    • Related Report
      2011 Final Research Report
  • [Journal Article] The role of miR-150 in malignant lymphoma2011

    • Author(s)
      Waatanabe A, Tagawa H, Takahashi N, et al.
    • Journal Title

      Leukemia

      Volume: 25 Issue: 8 Pages: 1324-34

    • DOI

      10.1038/leu.2011.81

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of microRNA-150 as a tumor suppressor in malignant lymphoma.2011

    • Author(s)
      渡部敦, 田川博之, 他
    • Journal Title

      Leukemia

      Volume: 印刷中(未定)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [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
    • Journal Title

      Blood

      Volume: 115 Pages: 4569-79

    • Related Report
      2011 Final Research Report
  • [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
    • Journal Title

      Blood

      Volume: 114 Pages: 3265-74

    • Related Report
      2011 Final Research Report
  • [Journal Article] Aberrant overexpression of microRNAs activate AKT signaling via down regulation of tumor suppressors in natural killer-cell lymphoma/leukemia2009

    • Author(s)
      Yamanaka Y, Tagawa H, et al
    • Journal Title

      Blood 114

      Pages: 3265-3275

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [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
    • Journal Title

      Blood

      Volume: (in press)

    • Related Report
      2011 Final Research Report
  • [Presentation] Oncogenic microRNAs in malignant lymphoma2010

    • Author(s)
      田川博之
    • Organizer
      NK腫瘍研究会
    • Place of Presentation
      東京ベルサーレ八重洲
    • Year and Date
      2010-03-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] Aberrant microRNA expressions activate AKT signaling in NK/T cell lymphoma/leukemia2009

    • Author(s)
      田川博之
    • Organizer
      日本がん学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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