Methyl-CpG Binding Protein 2 as a Potential Diagnostic and Prognostic Marker Facilitates Glioma Progression Through Activation of Wnt/β-Catenin Pathway

Abstract

Glioma is the primary malignant tumor in the central nervous system and has high malignancy, mortality, and recurrence rates. Because of its heterogeneity and drug resistance, the blood-brain barrier, and other factors, the treatment of glioma has mainly been surgical resection combined with traditional radiotherapy and chemotherapy. However, the therapeutic effect has not been satisfactory. Methyl-CpG binding protein 2 (MeCP2) is an epigenetic regulator that has been reported to regulate the initiation and progression of glioma. However, the underlying mechanism in glioma has remained unclear. The gene expression of MeCp2, miR-138-5p, the epithelial-mesenchymal transition, the apoptosis-related gene, and the Wnt/β-Catenin pathway-related gene and proliferation were detected by reverse transcription-quantitative polymerase chain reaction or Western blot. The cell proliferation and apoptosis of the glioma cell was assessed using the CCK-8 assay and flow cytometry assay. The relationship between miR-138-5p and MeCp2 was measured using the dual luciferase reporter assay. The effect of MeCp2 in U87 cells was examined in a xenograft tumorigenesis model in vivo. In our study, we found that MeCP2 was upregulated in glioma tissues and cell lines and that MeCP2 knockdown repressed cell proliferation and epithelial-mesenchymal transition but boosted cell apoptosis in glioma. Furthermore, MeCP2 knockdown attenuated in vivo glioma growth in a mice model. Mechanistically, miR-138-5p hindered the expression of MeCP2 by target MeCP2 and then inactivated the Wnt/β-catenin signaling pathway. In addition, subsequent rescue assays disclosed that miR-138-5p repressed the glioma malignant phenotype and MeCP2 overexpression reversed the inhibitory effect of miR-138-5p upregulation. Consistently, overexpression of MeCP2 elevated glioma development. However, inhibition of the Wnt/β-catenin signaling pathway with XAV-939 rescued the facilitation effect by overexpressing miR-138-5p. Our results have revealed that miR-138-5p/MeCP2/Wnt/β-catenin signaling might be a new target axis for glioma treatment strategies.