Detection of aberrant miRNA expression of malignant lymphoma

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591191
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Akita 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
• Keywords: microRNA / NK/T cell lymphoma

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.

Research Products

• [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
• [Journal Article] Aberrant expression of microRNA and its role in malignant lymphoma (2011)
  • Author(s): Tagawa H
  • Journal Title: Rinsho Ketsueki Volume: 52 Pages: 263-71
• [Journal Article] CpG-ODN 2006 and human parvovirus B19 genome consensus sequences selectively inhibit growth and development of erythroid progenitor cells (2010)
  • 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
• [Journal Article] Aberrant overexpression of microRNAs activate AKT signaling via downregulation of tumor suppressors in NK-cell lymphoma/leukemia (2009)
  • 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
• [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)