RNA-Binding Motif Protein RBM47 Promotes Invasiveness of Glioblastoma Through Activation of Epithelial-to-Mesenchymal Transition Program.

Abstract

Background: RNA-binding motif proteins (RBMs) have been widely implicated in the tumorigenesis of multiple human cancers but rarely investigated in glioblastoma (GBM). Methods: The expression level of RBM47 and its correlation with prognosis of GBM were examined using bioinformatics, quantitative reverse transcription PCR, and Western blot analysis. The colony formation assay and Cell Counting Kit-8 assay were used to determine the biological role of RBM47 in GBM. To measure invasiveness we used the wound healing assay and transwell assay. The regulatory relationship between RBM47 and the epithelial-to-mesenchymal transition (EMT) was examined by Western blot analysis and bioinformatic analysis. Results: Through integrative analysis of clinical proteomic and genomic tumor datasets, we found that RBM47 is significantly upregulated in GBM mesenchymal subtype, and its high expression is correlated with poor prognosis. In in vitro biological experiments, we observed a significant inhibitory effect of RBM47 knockdown on colony formation and cell growth using GBM cell lines. Conversely, overexpression of RBM47 restored and accelerated these processes. Moreover, in vitro, wound healing assays demonstrated the role of RBM46 in promoting and cell migration and invasion. Mechanistically, RBM47 enhances invasive capacity through the activation of the EMT program. In RBM47-knockdown cells, the expression levels of Vimentin and CD44 were suppressed, and the level of E-cadherin was increased. Conclusions: Taken together our results demonstrate the tumor promoting characteristics of RBM46 and suggest that it could be used both as a therapeutic target and prognostically.