title: 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.
authors.affiliation: Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 West Road of Riverside, Guangzhou, 510120, China.|Department of Neurosurgery, Guangzhou Women and Children's Medical Center, No. 9 Jinsui Road, Guangzhou, 510623, China.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 West Road of Riverside, Guangzhou, 510120, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, China.
authors.forename: Xi-Zhao
authors.initials: XZ
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 West Road of Riverside, Guangzhou, 510120, China.|Department of Neurosurgery, Guangzhou Women and Children's Medical Center, No. 9 Jinsui Road, Guangzhou, 510623, China.
authors.forename: Jun-Liang
authors.initials: JL
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Guangzhou Women and Children's Medical Center, No. 9 Jinsui Road, Guangzhou, 510623, China.
authors.forename: Xin-Ke
authors.initials: XK
authors.lastname: Xu
authors.affiliation: Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 West Road of Riverside, Guangzhou, 510120, China.
authors.forename: Hai-Gang
authors.initials: HG
authors.lastname: Li
authors.affiliation: Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 West Road of Riverside, Guangzhou, 510120, China.
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of GuangDong Pharmaceutical University, No. 167 Xingang Xi Road, Guangzhou, 510275, China.
authors.forename: Bai-Hui
authors.initials: BH
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, China. jiaweih@mail.sysu.edu.cn.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
authors.affiliation: Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 West Road of Riverside, Guangzhou, 510120, China. lefangcgz@yeah.net.|Department of Neurosurgery, Guangzhou Women and Children's Medical Center, No. 9 Jinsui Road, Guangzhou, 510623, China. lefangcgz@yeah.net.
authors.forename: Fang-Cheng
authors.initials: FC
authors.lastname: Li
mesh_terms: D000199:Actins / Q000235:genetics; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007633:Keratins / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D016019:Survival Analysis; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000199:Actins; D014408:Biomarkers, Tumor; C554939:CPEB4 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; C492001:HSPA9 protein, human; D006360:Heat-Shock Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014746:Vimentin; D007633:Keratins
keywords: Astrocytic tumor; CPEB4; Prognosis; Vimentin