Abstract
BackgroundThe epithelial-to-mesenchymal transition (EMT) has been linked to the regulation of glioma progression. However, the underlying signaling mechanisms that regulate EMT are poorly understood.MethodsQuantitative real-time PCR (RT-qPCR) and western blot were performed to detect the expression of MeCP2 in glioma tissues and cell lines. MeCP2 functions were tested with cell immunofluorescence staining and western blot. For in vivo experiments, mouse xenograft model was used to investigate the effects of MeCP2 on glioma. ChIP and Co-IP were used to detect the relationships among MeCP2, miR-200c and Suv39H1.ResultsIn this study, we found that MeCP2 was frequently up-regulated in human glioma tissues and cell lines. MeCP2 knockdown remarkably induced cell epithelial phenotype and inhibited mesenchymal marker ZEB1 and ZEB2 in vitro and in vivo. In addition, MeCP2 in glioma tissues was negatively correlated with miR-200c expression, and miR-200c overexpression partially abrogated mesenchymal phenotype induced by MeCP2. More importantly, we showed that MeCP2 recruited H3K9 to the promoter of miR-200c by interacting with SUV39H1, resulting in EMT of glioma cells.ConclusionsThis study for the first time reveals MeCP2 as a novel regulator of EMT in glioma and suggest that MeCP2 inhibition may represent a promising therapeutic option for suppressing EMT in glioma.
Highlights
The epithelial-to-mesenchymal transition (EMT) has been linked to the regulation of glioma progression
Methyl CpG-binding protein 2 (MeCP2) protein expression was increased in glioma tissues compared with that in normal brain tissues (Fig. 1d-e)
To explore whether MeCP2 represses the level of miR-200c expression via H3K9me3 modification in glioma cells, and the results found that a significant enrichment of H3K9me3 in the miR-200c promoter was observed in MeCP2-overexpressed glioma cells compared with vector cells (Fig. 8a-c)
Summary
The epithelial-to-mesenchymal transition (EMT) has been linked to the regulation of glioma progression. Gliomas are the most common primary brain tumor characterized by highly infiltrative growth. Base on the pathological characteristics, gliomas can be classified into four clinical grades. (Glioblastoma multiforme, GBM) is one of the most aggressive types of brain tumors, and despite the combination of multiple treatments, including surgery, chemotherapy and radiation, patients often still develop refractory recurrence [1]. MeCP2 has been found to have two functional domains, a 104-amino-acid transcriptional repression domain (TRD) and an 85-amino-acid MBD. MeCP2 has been reported to be implicated in a number of molecular functions, such as transcription regulation, RNA splicing, and chromatin organization [11, 12]. Little is known about its biological characteristics and molecular mechanisms in human glioma
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