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.

<p>CircTTBK2 Contributes to the Progression of Glioma Through Regulating miR-145-5p/CPEB4 Axis</p>

“…Wang et al and Zhi et al manifested that CPEB4 level was enhanced in glioma and associated with worse prognosis. 16 , 17 Gu et al proved that CPEB4 level could be restrained by miR-98-5p and then participated in regulating cell migration, growth and apoptosis in glioma cells. 19 In line with these reports, in this project, CPEB4 level was raised in tumor tissues and cell lines.…”

“…15 As a member of the cytoplasmic polyadenylation element binding protein (CPEB) family, CPEB4 level has been verified to be elevated in glioma and related to the malignancy and dismal prognosis of glioma. 16 , 17 Previous studies also suggested that CPEB4 could be targeted by miRNAs, such as miR-30c-5p, 18 miR-98-5p, 19 miR-29c-5p 20 and miR-1246. 21 Nevertheless, the association between miR-145-5p and CPEB4 in glioma progression remains unexplored.…”

Unravelling gene regulation in the epidermis during differentiation

“…CPEB4 expression was found to be higher in glioma tissues as compared to their corresponding nonneoplastic brain tissues (Zhijun, Dapeng et al 2017). Here, the expression of CPEB4 correlated with the grade of clinical gliomas, making it an oncogenic promoter in glioblastomas (Zhijun, Dapeng et al 2017). Hence, the altered expression of CPEB4 in different cancers suggest its complicated role in tumorigenesis.…”

“…The role of CPEB4 was accessed in hepatocellular carcinoma (HCC) and the protein levels of CPEB4 were found to be higher in early-stage HCC compared to late-stage HCC patients (Tsai, Chang et al 2016). CPEB4 expression was found to be higher in glioma tissues as compared to their corresponding nonneoplastic brain tissues (Zhijun, Dapeng et al 2017). Here, the expression of CPEB4 correlated with the grade of clinical gliomas, making it an oncogenic promoter in glioblastomas (Zhijun, Dapeng et al 2017).…”

“…Other studies have demonstrated CPEB4 to be associated with tumour progression (Tsai, Chang et al 2016, Hu, Zhang et al 2017, Zhijun, Dapeng et al 2017. The role of CPEB4 was accessed in hepatocellular carcinoma (HCC) and the protein levels of CPEB4 were found to be higher in early-stage HCC compared to late-stage HCC patients (Tsai, Chang et al 2016).…”