title: 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.
authors.affiliation: 1 Department of Neurosurgery, Huaihe Hospital of Henan University, Kaifeng, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Zhijun
authors.affiliation: 2 Department of Radiotherapy, Huaihe Hospital of Henan University, Kaifeng, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Dapeng
authors.affiliation: 3 Department of Pathology, Huaihe Hospital of Henan University, Kaifeng, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hong
authors.affiliation: 1 Department of Neurosurgery, Huaihe Hospital of Henan University, Kaifeng, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Guicong
authors.affiliation: 1 Department of Neurosurgery, Huaihe Hospital of Henan University, Kaifeng, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Bingjian
authors.affiliation: 1 Department of Neurosurgery, Huaihe Hospital of Henan University, Kaifeng, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Honglin
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D005910:Glioma / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000032:analysis / Q000502:physiology*
chemical_list: C554939:CPEB4 protein, human; D016601:RNA-Binding Proteins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Cytoplasmic polyadenylation element binding protein 4; glioma; invasion; migration; prognosis