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

Abstract

AbstractBackgroundHOXgenes 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.ResultsIn this study, we found high expression of theHOXD9gene 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 ofHOXD9in gliomas, we silenced its expression in the glioma cell line U87 usingHOXD9-specific siRNA, and observed decreased cell proliferation, cell cycle arrest, and induction of apoptosis. It was suggested thatHOXD9contributes to both cell proliferation and/or cell survival. TheHOXD9gene 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.HOXD9siRNA 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 ofHOXD9in GCSCs compared with normal astrocyte cells and neural stem/progenitor cells (NSPCs).ConclusionsOur results suggest thatHOXD9may 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.