Methyl-CpG Binding Protein 2 as a Potential Diagnostic and Prognostic Marker Facilitates Glioma Progression Through Activation of Wnt/I3-Catenin Pathway

BACKGROUND: Glioma is the primary malignant tumor in the central nervous system and has high malignancy, neity 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. METHODS: The gene expression of MeCp2, miR-138-5p, the epithelial-mesenchymal transition, the apoptosisrelated gene, and the Wnt/b-Catenin pathway-related gene and proliferation were detected by reverse transcriptionquantitative 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. RESULTS: In our study, we found that MeCP2 was -pregulated in glioma tissues and cell lines and that MeCP2 knockdown repressed cell proliferation and epithelial-mesenchymal transition but boosted cell apoptosis vivo glioma growth in a mice model. Mechanistically, miR 138-5p hindered the expression of MeCP2 by target MeCP2 and then inactivated the Wnt/b-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/b-catenin signaling pathway with XAV-939 rescued the facilitation effect by overexpressing miR-138-5p. -CONCLUSIONS: Our results have revealed that miR-138-5p/MeCP2/Wnt/b-catenin signaling might be a new target axis for glioma treatment strategies.

Automated summary

The miR-138-5p/MeCP2/Wnt/b-catenin signaling pathway may serve as a new target for glioma treatment.