BackgroundGliomas are one of the most common malignant brain tumors and bring a big threat to human life as traditional therapy is unsatisfactory. RBM5 was a RNA-binding motif protein and was reported as a tumor suppressor. But the role of RBM5 in gliomas was unknown.MethodsThe mRNA level of RBM5 was determined in gliomas tissues and cell lines by real-time quantitative PCR (qRT-PCR) assay while the association of RBM5 expression with prognosis was analyzed by Kaplan-Meier method and compared by log-rank test. Lentivirus was used to overexpress RBM5 in gliomas cells. MTT and BrdU incorporation assay were used to determine cell proliferation and DNA synthesis when the ability of cell migration and invasion was analyzed by transwell assay with/without Matrigel. Cell apoptosis rate was determined with fluorescence-activated cell sorting (FACS) method. Then, expression of apoptosis molecules and critical members in Wnt/β-catenin pathway were detected by western blot analysis.ResultsRBM5 was shown to be downregulated in gliomas tissues and gliomas cell lines. And decreased RBM5 expression was clinically correlated with tumor stage, patient age, and poor prognosis of gliomas patients. The proliferation and DNA synthesis was dramatically inhibited when RBM5 was overexpressed in SHG44 or U251 cells. Also, the ability of cell migration and invasion was disrupted. Then, the level of β-catenin and Cyclin D1 significantly decreased when DKK1 and P-GSK-3β increased reversely in SHG44 cells, which suggested that RBM5 inhibited canonical Wnt/β-catenin signaling. Meanwhile, we demonstrated that caspase3-mediated apoptotic pathway was activated by RBM5 as Bax, TNF-α, and cleaved caspase3 were greatly upregulated while antiapoptotic molecule Bcl-2 was downregulated. Additionally, that apoptotic rate increased significantly from less than 1 to 32% in RBM5-overexpressed SHG44 cells further supported the pro-apoptosis role of RBM5 in gliomas cells.ConclusionsRBM5 plays a suppressor role in human gliomas by inhibiting Wnt/β-catenin signaling and inducing cell apoptosis. This study improves our knowledge about the carcinogenesis and progression of human gliomas, which would greatly contribute to the therapy for gliomas patients.

In this study, we analyzed the prognostic value of epithelial membrane protein 3 (EMP3) in terms of overall survival (OS) in glioblastoma multiforme (GBM) and the association between its expression and DNA methylation.Bioinformatic analysis was performed by using data from the Cancer Genome Atlas (TCGA) database.EMP3 expression was markedly higher in GBM tissues than in normal brain tissues. High EMP3 expression was associated with significantly worse OS in patients with GBM. Univariate and multivariate analysis showed that EMP3 expression was an independent prognostic factor of poor OS no matter converting its expression into categorical variables (Hazard Ratio [HR] = 1.359, 95%CI: 1.118–1.652, P = .002) or setting it as a continuous variable (HR = 1.178, 95%CI: 1.101–1.260, P < .001). Among different subtypes of GBM, proneural subtype had the lowest EMP3 expression. The lowest EMP3 expression was observed in cluster 5 DNA methylation, which all belong to G-CIMP phenotype. Regression analysis confirmed a moderate negative correlation between EMP3 expression and its DNA methylation (Pearson's r = −0.61).Based on these findings, we infer that high EMP3 expression might be an independent indicator of unfavorable OS in GBM. EMP3 expression might be repressed by DNA methylation.

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