C/EBPß expression decreases in cervical cancer and leads to tumorigenesis.

ABSTRACT

BACKGROUND: Cervical cancer is currently estimated to be the fourth most common cancer among women worldwide and the leading cause of cancer-related deaths in some of the world's poorest countries. C/EBPß has tumor suppressor effects because it is necessary for oncogene-induced senescence. However, C/EBPß also has an oncogenic role. The specific role of C/EBPß in cervical cancer as a tumor suppressor or oncoprotein is unclear. OBJECTIVE: To explore the role of the C/EBPß protein in cervical tumorigenesis and progression. METHODS: Quantitative RT-PCR was used to analyze C/EBPß (15 cervical cancer tissue samples and 15 corresponding normal cervical tissue samples), miR-661, and MTA1 mRNA expression in clinical samples (10 cervical cancer tissue samples and 10 corresponding normal cervical tissue samples). Immunohistochemistry was used to analyze C/EBPß (381 clinical samples), Ki67 (80 clinical samples) and PCNA ( 60 clinical samples) protein expression. MALDI-TOF MassARRAY was used to analyze C/EBPß gene methylation (13 cervical cancer tissues and 13 corresponding normal cervical tissues). Cell proliferation was analyzed by CCK-8 in cervical cancer cell lines. Western blotting and immunohistochemistry were performed to detect C/EBPß protein expression levels, and mRNA expression was analyzed by quantitative RT-PCR analysis. Flow cytometry was performed to measure cell cycle distribution and cell apoptosis. Colony formation, Transwell, cell invasion, and wound healing assays were performed to detect cell migration and invasion. RESULTS: C/EBPß protein expression was significantly reduced in cervical cancer tissues compared with cervicitis tissues (P < 0.01). Ki67 protein and PCNA protein expression levels were significantly higher in cervical cancer tissues compared with cervicitis tissues. The rate of C/EBPß gene promoter methylation of CpG12, 13, 14 and CpG19 in cervical cancer tissues was significantly increased compared with normal cervical tissue (P < 0.05). In addition, C/EBPß was overexpressed in cervical cancer cells and this overexpression inhibited cell proliferation, migration, invasion, arrested cells in S phase, and promoted apoptosis. CONCLUSIONS: We have demonstrated that C/EBPß decreased in cervical cancer tissues and overexpression of the C/EBPß gene in cervical cancer cells could inhibit proliferation, invasion and migration.