Abstract
DNA methylation and histone acetylation are important epigenetic regulators of gene expression in cancer. Histone methylation has recently been proven to be a reversible process regulated by lysine (K)-specific demethylase 1A (KDM1A/LSD1). We previously reported that KDM1A expression in primary medulloblastomas is correlated with adverse patient outcome. Growth and migration of medulloblastoma cells was reduced after siRNA-mediated knockdown of KDM1A in vitro in a modified wound-healing assay. KDM1A inhibition using the MAO inhibitor, tranylcypromine, resulted in increased global H3K4 methylation and inhibited growth of MB cells. Medulloblastoma has been suggested to arise from the external granular cell layer (EGL) of the developing cerebellum. Interestingly, KDM1A mRNA was significantly upregulated in these granular cell precursors (GCPs) derived from various mouse lines at the time when GCPs normally migrate from the EGL to the internal granule layer. Our results suggest that KDM1A is not only over-expressed in medulloblastoma, but may play an important role in migration of medulloblastoma cells and their progenitors.
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