title: Biphasic and Stage-Associated Expression of CPEB4 in Hepatocellular Carcinoma.
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.
authors.affiliation: Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
authors.forename: Li-Yun
authors.initials: LY
authors.lastname: Tsai
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Chang
authors.affiliation: Department of Surgery, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan.
authors.forename: Ming-Che
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
authors.forename: Ying-Chen
authors.initials: YC
authors.lastname: Chang
authors.affiliation: General Manager, Mao Ying Genetech Inc., Taipei, Taiwan.
authors.forename: Pei-Ing
authors.initials: PI
authors.lastname: Hwang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Yi-Shuian
authors.initials: YS
authors.lastname: Huang
authors.affiliation: Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.|Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|Department of Pediatrics, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan.
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D005260:Female; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: C554939:CPEB4 protein, human; D016601:RNA-Binding Proteins