Abstract
Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a sequence-specific RNA-binding protein and translational regulator, with expression associated with tumor progression. Nevertheless, CPEB4 seems to play paradoxical roles in cancers–an oncogenic promoter in pancreatic ductal adenocarcinoma (PDA) and glioblastomas but a tumor suppressor in hepatocellular carcinoma (HCC). To assess whether CPEB4-regulated carcinogenesis is tissue-specific, we reevaluated the role of CPEB4 in HCC. Although proliferation of hepatocytes appeared normal in CPEB4-knockout (KO) mice after partial hepatectomy, knockdown (KD) of CPEB4 in HepG2 liver cancer cells promoted colony formation in vitro. Moreover, the growth of CPEB4-KD cells was accelerated in an in vivo xenograft mouse model. In tumorous and adjacent non-tumorous paired liver specimens from 49 HCC patients, the protein level of CPEB4 was significantly upregulated in early-stage HCC but decreased toward late-stage HCC. This finding agrees with changes in CPEB4 mRNA level from analysis of two sets of HCC microarray data from the Gene Expression Omnibus (GEO) database. Taken together, downregulation of CPEB4 likely occurs at the late cancer stage to facilitate HCC progression. Biphasic alteration of CPEB4 expression during HCC progression suggests its complicated role in tumorigenesis.
Highlights
Many processes involved in tumor development are due to dysregulated gene expression [1].Transcription factors such as p53, E2F and Twist were found to suppress and/or promote cancers [2,3,4]
Because Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is expressed in the adult liver and its downreguation is correlated with hepatocellular carcinoma (HCC) progression [27], here, we used
CPEB4 was first identified as a pro-oncogenic factor and promoted translation of tissue plasminogen activator RNA to support metastatic invasion of pancreatic cancer cells [26]
Summary
Many processes involved in tumor development are due to dysregulated gene expression [1]. Transcription factors such as p53, E2F and Twist were found to suppress and/or promote cancers [2,3,4]. Translational control in carcinogenesis has gained increasing attention because regulated translation of mRNAs is important to keep cell cycle in check [5,6,7]. Aberrant expression and phosphoryation of some key players in the translational apparatus, such as eukaryotic initiation factor (eIF)4E and eIF4E-binding proteins (4EBPs), enhances the malignancy of cells [8, 9]. Fragile X mental retardation protein and CPEBs, RNA-binding.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
