CPEB4 interacts with Vimentin and involves in progressive features and poor prognosis of patients with astrocytic tumors

Abstract

Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a regulator of gene transcription and has been reported to be associated with biological malignancy in cancers. However, it is unclear whether CPEB4 has any clinical significance in patients with astrocytic tumors, and mechanisms that CPEB4 contribute to progression of astrocytic tumors remain largely unknown. Here, correlation between CPEB4 expression and prognosis of patients with astrocytic tumors were explored by using qPCR, WB and IHC, and X-tile, SPSS software. Cell lines U251 MG and A172 were used to study CPEB4's function and mechanisms. Co-immunoprecipitation, mass spectrometry, immunofluorescent assay, and western blot were performed to observe the interaction between CPEB4 and Vimentin. CPEB4 mRNA and protein levels were markedly elevated in 12/12 astrocytic tumors in comparison to paratumor. High expression of CPEB4 was significantly correlated with clinical progressive futures and work as an independent adverse prognostic factor for overall survival of patients with astrocytic tumors (relative risk 4.5, 95 % CI 2.1-11.2, p = 0.001). Moreover, knockdown of CPEB4 in astrocytic tumor cells inhibited their proliferation ability , clonogenicity, and invasiveness. Five candidate proteins, GRP78, Mortalin, Keratin, Vimentin, and β-actin, were identified, and the interaction between CPEB4 and Vimentin was finally confirmed. Downregulation of CPEB4 could reduce the protein expression of Vimentin. Our studies first validated that CPEB4 interacts with Vimentin and indicated that high CPEB4 expression in astrocytic tumors correlates closely with a clinically aggressive future, and that CPEB4 might represent a valuable prognostic marker for patients with astrocytic tumors.

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

“…CPEB4 has emerged as a potential biomarker in several cancers, such as colorectal cancer, breast cancer, astrocytic tumor, non-small cell lung cancer, pancreatic cancer, and glioma. [18][19][20][21][22][23][24] In this study, we found that compared to adjacent normal brain tissues, CPEB4 protein and mRNA levels were significantly increased in glioma tissues. In addition, CPEB4 expression was positively correlated with advanced WHO grade (p < 0.001) and lower KPS score (p < 0.001).…”

Regulation of the Expression of Cytoplasmic Polyadenylation Element Binding Proteins for the Treatment of Cancer

“…CPEB4-associated mRNAs are significantly enriched in multiple cellular functions that are relevant to tumorigenesis, including Ras-related molecules, cell signaling components, chromatin remodeling proteins, cyclins, apoptosis-related molecules, stress and inflammation factors, metabolic enzymes and genes related to cell migration and metastasis (19). In addition, CPEB4 has been reported in association with tumor growth, vascularization and invasion in invasive ductal breast carcinoma (IDC), colorectal cancer, pancreatic ductal adenocarcinoma, metastatic prostate cancer and glioblastoma (19,(49)(50)(51)(52). High expression of CPEB4 has been observed in 48.6% of IDC samples and is possibly related to increased histological grading and N stage of IDC (50).…”

“…Suppression of CPEB4 expression by siRNA in SW480 and LOVO colon cancer cells enhances apoptosis and decreases cellular proliferation and is associated with decreased expression of antiapoptotic protein Bcl-X and increased expression of proapoptotic protein Bax (52). CPEB4 is also overexpressed in glioblastomas but not expressed in normal astrocytes or paratumor tissues (19,49). CPEB4 down-regulation in glioma cells results in reduced tumor size, cellular proliferation and microvessel density, as well as increased apoptosis (19,49,54).…”

“…CPEB4 is also overexpressed in glioblastomas but not expressed in normal astrocytes or paratumor tissues (19,49). CPEB4 down-regulation in glioma cells results in reduced tumor size, cellular proliferation and microvessel density, as well as increased apoptosis (19,49,54). In addition, glioma cells with CPEB4 suppression have reduced vimentin expression and decreased invasiveness than the control cells, thus indicating that high CPEB4 expression in astrocytic tumors correlates with a clinically aggressive feature (49,54).…”

“…CPEB4 down-regulation in glioma cells results in reduced tumor size, cellular proliferation and microvessel density, as well as increased apoptosis (19,49,54). In addition, glioma cells with CPEB4 suppression have reduced vimentin expression and decreased invasiveness than the control cells, thus indicating that high CPEB4 expression in astrocytic tumors correlates with a clinically aggressive feature (49,54). Moreover, CPEB4 also regulates the glioma stem cells, whereas suppression of CPEB4 expression inhibits the growth, proliferation and invasion of glioma stem cells (54).…”