1050

CEBPA

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-alpha (C/EBPalpha) is a transcriptional regulator with an essential role in tumor metastasis. We used short-activating RNAs (saRNA) to enhance expression of C/EBPalpha. Intravenous injection of C/EBPalpha-saRNA in a nude mouse liver orthotopic xenograft tumor model inhibited intrahepatic and distant metastasis. C/EBPalpha-saRNA-treated mice showed increased serum levels of albumin and decreased alanine aminotransferase (ALT), glutamic-oxalacetic transaminase (AST), indicating a role of C/EBPalpha in improving liver function. Migration and invasion were inhibited in hepatoma cell lines transfected with C/EBPalpha-saRNA. We also observed an inhibition of epithelial-mesenchymal transition (EMT) and suppression of epidermal growth factor receptor (EGFR), EGFR phosphorylation, and beta-catenin in C/EBPa-saRNA-transfected cells. Our results suggested that C/EBPalpha-saRNA successfully inhibited HCC metastasis by inhibiting EGFR/beta-catenin signaling pathway mediated EMT in vitro and in vivo.

BACKGROUND/AIMS: The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) is a basic leucine zipper transcription factor that plays essential roles in tumor progression. Although decreased or absent C/EBPalpha expression in many cancers suggests a possible role for C/EBPalpha as a tumor suppressor, the functions of C/EBPalpha in lung adenocarcinoma remain unclear. METHODS: Here, C/EBPalpha expression levels in 26 lung adenocarcinoma and para-carcinoma tissue samples were detected by qRT-PCR and immunohistochemistry. Cell transwell assays, wound healing assay and three-dimensional spheroid invasion assay were performed to assess the effects of C/EBPalpha on migration and invasion in lung adenocarcinoma cells in vitro. Western blotting was applied to analyze the potential mechanisms. RESULTS: C/EBPalpha was found to be decreased in lung adenocarcinoma tissues compared to para-carcinoma tissues. Overexpression of C/EBPalpha significantly inhibited the migration and invasion of lung adenocarcinoma cells. In addition, C/EBPalpha overexpression suppressed the epithelial-mesenchymal transition (EMT) that was characterized by a gain of epithelial and loss of mesenchymal markers. Further study showed that C/EBPalpha suppressed the transcription of beta-catenin and downregulated the levels of its downstream targets. CONCLUSION: Our data suggest that C/EBPalpha inhibits lung adenocarcinoma cell invasion and migration by suppressing beta-catenin-mediated EMT in vitro. Thus, C/EBPalpha may be helpful as a potential target for treatment of lung adenocarcinoma.CI - (c) 2017 The Author(s). Published by S. Karger AG, Basel.