Overexpression of CPEB4 in glioma indicates a poor prognosis by promoting cell migration and invasion.

Abstract

Glioma is an aggressive malignancy with limited effective treatment and poor prognosis. Cytoplasmic polyadenylation element binding protein 4 is a regulator of gene transcription and has been reported to be associated with biological malignancy in cancers. However, the mechanisms that cytoplasmic polyadenylation element binding protein 4 contributes to tumor migration and invasion remain unknown. Here, cytoplasmic polyadenylation element binding protein 4 expression was assessed using immunohistochemistry, and the results were compared with clinicopathological parameters, including survival. Using glioma cell lines (SKMG-4 and T98G), we measured cytoplasmic polyadenylation element binding protein 4 messenger RNA and protein expression and studied the effects of cytoplasmic polyadenylation element binding protein 4 expression on cell migration and invasion. Cytoplasmic polyadenylation element binding protein 4 expression was significantly higher in tumor tissues than that in normal brain tissues. Clinicopathological analysis showed that cytoplasmic polyadenylation element binding protein 4 expression was significantly correlated with advanced World Health Organization grade ( p < 0.001) and lower Karnofsky Performance Status (KPS) score ( p = 0.001). Cytoplasmic polyadenylation element binding protein 4 positive as opposed to the cytoplasmic polyadenylation element binding protein 4 negative patients had lower overall survival ( p < 0.001). Multivariate analysis suggested that cytoplasmic polyadenylation element binding protein 4 expression might be an independent prognostic indicator (hazard ratio = 2.091, 95% confidence interval: 1.093-3.999, p = 0.026) for glioma patients. Moreover, upregulated cytoplasmic polyadenylation element binding protein 4 expression could promote T98G cell migration and invasion, and downregulated cytoplasmic polyadenylation element binding protein 4 expression could inhibit SKMG-4 cell migration and invasion. Furthermore, downregulated cytoplasmic polyadenylation element binding protein 4 could reduce the protein expression of matrix metalloproteinase-2 and matrix metalloproteinase-9. In conclusion, our studies indicated that positive cytoplasmic polyadenylation element binding protein 4 expression predicted a worse prognosis in glioma patients, and cytoplasmic polyadenylation element binding protein 4 could represent a useful biomarker or therapeutic target for glioma.