Functional analysis of HOXD9 in human gliomas and glioma cancer stem cells

Masanao Tabuse, Shigeki Ota, Yohei Ohashi, Raita Fukaya, Aya Misawa, Kazunari Yoshida, Takeshi Kawase, Hideyuki Saya, Cécile Thirant, Hérve Chneiweiss, Yumi Matsuzaki, Hideyuki Okano, Yutaka Kawakami, Masahiro Toda

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background: HOX genes encode a family of homeodomain-containing transcription factors involved in the determination of cell fate and identity during embryonic development. They also behave as oncogenes in some malignancies.Results: In this study, we found high expression of the HOXD9 gene transcript in glioma cell lines and human glioma tissues by quantitative real-time PCR. Using immunohistochemistry, we observed HOXD9 protein expression in human brain tumor tissues, including astrocytomas and glioblastomas. To investigate the role of HOXD9 in gliomas, we silenced its expression in the glioma cell line U87 using HOXD9-specific siRNA, and observed decreased cell proliferation, cell cycle arrest, and induction of apoptosis. It was suggested that HOXD9 contributes to both cell proliferation and/or cell survival. The HOXD9 gene was highly expressed in a side population (SP) of SK-MG-1 cells that was previously identified as an enriched-cell fraction of glioma cancer stem-like cells. HOXD9 siRNA treatment of SK-MG-1 SP cells resulted in reduced cell proliferation. Finally, we cultured human glioma cancer stem cells (GCSCs) from patient specimens found with high expression of HOXD9 in GCSCs compared with normal astrocyte cells and neural stem/progenitor cells (NSPCs).Conclusions: Our results suggest that HOXD9 may be a novel marker of GCSCs and cell proliferation and/or survival factor in gliomas and glioma cancer stem-like cells, and a potential therapeutic target.

Original languageEnglish
Article number60
JournalMolecular Cancer
Volume10
DOIs
Publication statusPublished - 2011 May 22

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Neoplastic Stem Cells
Glioma
Cell Proliferation
Small Interfering RNA
Cell Survival
Stem Cells
Side-Population Cells
Cell Line
Astrocytoma
Glioblastoma
Cell Cycle Checkpoints
Oncogenes
Brain Neoplasms
Astrocytes
Genes
Embryonic Development
Real-Time Polymerase Chain Reaction
Transcription Factors
Immunohistochemistry
Apoptosis

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

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Functional analysis of HOXD9 in human gliomas and glioma cancer stem cells. / Tabuse, Masanao; Ota, Shigeki; Ohashi, Yohei; Fukaya, Raita; Misawa, Aya; Yoshida, Kazunari; Kawase, Takeshi; Saya, Hideyuki; Thirant, Cécile; Chneiweiss, Hérve; Matsuzaki, Yumi; Okano, Hideyuki; Kawakami, Yutaka; Toda, Masahiro.

In: Molecular Cancer, Vol. 10, 60, 22.05.2011.

Research output: Contribution to journalArticle

Tabuse, M, Ota, S, Ohashi, Y, Fukaya, R, Misawa, A, Yoshida, K, Kawase, T, Saya, H, Thirant, C, Chneiweiss, H, Matsuzaki, Y, Okano, H, Kawakami, Y & Toda, M 2011, 'Functional analysis of HOXD9 in human gliomas and glioma cancer stem cells', Molecular Cancer, vol. 10, 60. https://doi.org/10.1186/1476-4598-10-60
Tabuse, Masanao ; Ota, Shigeki ; Ohashi, Yohei ; Fukaya, Raita ; Misawa, Aya ; Yoshida, Kazunari ; Kawase, Takeshi ; Saya, Hideyuki ; Thirant, Cécile ; Chneiweiss, Hérve ; Matsuzaki, Yumi ; Okano, Hideyuki ; Kawakami, Yutaka ; Toda, Masahiro. / Functional analysis of HOXD9 in human gliomas and glioma cancer stem cells. In: Molecular Cancer. 2011 ; Vol. 10.
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