title: Functional analysis of HOXD9 in human gliomas and glioma cancer stem cells.
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.
authors: Neuroimmunology Research Group, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Masanao
authors: M
authors: Tabuse
authors: Shigeki
authors: S
authors: Ohta
authors: Yohei
authors: Y
authors: Ohashi
authors: Raita
authors: R
authors: Fukaya
authors: Aya
authors: A
authors: Misawa
authors: Kazunari
authors: K
authors: Yoshida
authors: Takeshi
authors: T
authors: Kawase
authors: Hideyuki
authors: H
authors: Saya
authors: Cécile
authors: C
authors: Thirant
authors: Hérve
authors: H
authors: Chneiweiss
authors: Yumi
authors: Y
authors: Matsuzaki
authors: Hideyuki
authors: H
authors: Okano
authors: Yutaka
authors: Y
authors: Kawakami
authors: Masahiro
authors: M
authors: Toda
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