CCAAT enhancer binding protein α suppresses proliferation, metastasis, and epithelial-mesenchymal transition of ovarian cancer cells via suppressing the Wnt/β-catenin signaling

Li-Mei Zhang, Mo Li, Chen-Chen Tian, Tong-Tong Wang,  Shu-Fang Mi

Abstract:

CCAAT enhancer-binding protein alpha (CEBPA, also known as C/EBPα) is a transcription factor that plays an essential role in regulating terminal differentiation and cell proliferation of many tissues. The objective of this study was to explore the potential function of CEBPA in ovarian cancer. The expression of CEBPA in ovarian cancer samples and adjacent normal tissues was evaluated by qRT-PCR. The putative role of CEBPA in ovarian cancer cells was evaluated by immunohistochemistry, western blot, cell viability assay, BrdU incorporation assay, soft agar colony formation assay, Transwell cell migration and invasion assay, tumor xenograft formation, and lung metastasis model. We found that CEBPA was downregulated in ovarian cancer samples and predicted a poor prognosis. CRISPR/Cas9-mediated CEBPA knockout promoted proliferation, anchorage-independent growth, migration, invasion, and EMT of ovarian cancer cells, while enforced CEPBA expression suppressed proliferation, anchorage-independent growth, migration, invasion, EMT, tumor xenograft growth, and lung metastasis of ovarian cancer cells. Furthermore, we found that the knockout of CEBPA activated Wnt/β-catenin signaling in ovarian cancer cells, while CEBPA overexpression suppressed Wnt/β-catenin activation. Our data indicated that CEBPA acted as a tumor suppressor in ovarian cancer, and might be a potential prognostic marker for ovarian cancer treatment.