title: C/EBPα Short-Activating RNA Suppresses Metastasis of Hepatocellular Carcinoma through Inhibiting EGFR/β-Catenin Signaling Mediated EMT.
abstract: Hepatocellular carcinoma is associated with high mortality, and tumor metastasis is an important reason for poor prognosis. However, metastasis has not been effectively prevented in clinical therapy and the mechanisms underlying metastasis have not been fully characterized. CCAAT/enhancer-binding protein-α (C/EBPα) is a transcriptional regulator with an essential role in tumor metastasis. We used short-activating RNAs (saRNA) to enhance expression of C/EBPα. Intravenous injection of C/EBPα-saRNA in a nude mouse liver orthotopic xenograft tumor model inhibited intrahepatic and distant metastasis. C/EBPα-saRNA-treated mice showed increased serum levels of albumin and decreased alanine aminotransferase (ALT), glutamic-oxalacetic transaminase (AST), indicating a role of C/EBPα in improving liver function. Migration and invasion were inhibited in hepatoma cell lines transfected with C/EBPα-saRNA. We also observed an inhibition of epithelial-mesenchymal transition (EMT) and suppression of epidermal growth factor receptor (EGFR), EGFR phosphorylation, and β-catenin in C/EBPa-saRNA-transfected cells. Our results suggested that C/EBPα-saRNA successfully inhibited HCC metastasis by inhibiting EGFR/β-catenin signaling pathway mediated EMT in vitro and in vivo.
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Huan
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wen
authors.affiliation: Laboratory of Biotherapy of Cancer, Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wu
authors.affiliation: General Surgery Center, Chengdu Military General Hospital, Chengdu, Sichuan Province, China.
authors.forename: Weihui
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Nagy A
authors.initials: NA
authors.lastname: Habib
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Bie
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xia
mesh_terms: D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D066246:ErbB Receptors / Q000502:physiology*; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D012313:RNA / Q000008:administration & dosage*; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D051176:beta Catenin; D012313:RNA; D066246:ErbB Receptors