PMID- 27158894 OWN - NLM STAT- MEDLINE DCOM- 20170726 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 5 DP - 2016 TI - Biphasic and Stage-Associated Expression of CPEB4 in Hepatocellular Carcinoma. PG - e0155025 LID - 10.1371/journal.pone.0155025 [doi] LID - e0155025 AB - 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. FAU - Tsai, Li-Yun AU - Tsai LY AD - Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan. FAU - Chang, Yu-Wei AU - Chang YW AD - Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. FAU - Lee, Ming-Che AU - Lee MC AD - Department of Surgery, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan. FAU - Chang, Ying-Chen AU - Chang YC AD - Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan. FAU - Hwang, Pei-Ing AU - Hwang PI AD - General Manager, Mao Ying Genetech Inc., Taipei, Taiwan. FAU - Huang, Yi-Shuian AU - Huang YS AD - Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. FAU - Cheng, Ching-Feng AU - Cheng CF AD - Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan. AD - Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. AD - Department of Pediatrics, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160509 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (CPEB4 protein, human) RN - 0 (RNA-Binding Proteins) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Animals MH - Carcinoma, Hepatocellular/*metabolism MH - Female MH - Heterografts MH - Humans MH - Liver Neoplasms/*metabolism MH - Male MH - Mice MH - Mice, Knockout MH - Middle Aged MH - RNA-Binding Proteins/genetics/immunology/*metabolism PMC - PMC4861299 COIS- Competing Interests: PeiIng Hwang is employed by Mao Ying Genetech Inc. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. EDAT- 2016/05/10 06:00 MHDA- 2017/07/27 06:00 PMCR- 2016/05/09 CRDT- 2016/05/10 06:00 PHST- 2015/11/01 00:00 [received] PHST- 2016/04/22 00:00 [accepted] PHST- 2016/05/10 06:00 [entrez] PHST- 2016/05/10 06:00 [pubmed] PHST- 2017/07/27 06:00 [medline] PHST- 2016/05/09 00:00 [pmc-release] AID - PONE-D-15-47842 [pii] AID - 10.1371/journal.pone.0155025 [doi] PST - epublish SO - PLoS One. 2016 May 9;11(5):e0155025. doi: 10.1371/journal.pone.0155025. eCollection 2016.