机构：[1]Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China,[2]Laboratory of Biotherapy of Cancer, Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China,[3]General Surgery Center, Chengdu Military General Hospital, Chengdu, Sichuan Province, China,[4]Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
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.
基金：
National
Natural Sciences Foundation of China (No.
81272224),
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2016]版：
大类|3 区生物
小类|3 区综合性期刊
最新[2023]版：
大类|3 区综合性期刊
小类|3 区综合性期刊
第一作者：
第一作者机构：[1]Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China,
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Huan Hongbo,Wen Xudong,Chen Xuejiao,et al.C/EBPα Short-Activating RNA Suppresses Metastasis of Hepatocellular Carcinoma through Inhibiting EGFR/β-Catenin Signaling Mediated EMT.[J].PloS one.2016,11(4):e0153117.doi:10.1371/journal.pone.0153117.
