FOXA1 is associated with malignant tumors, but its function in epithelial ovarian carcinoma (EOC) remains unclear. HDAC3 can affect the proliferation, migration, and invasion capabilities of EOC cells. This study aimed to investigate the function of FOXA1 in ovarian cancer and the relationship between HDAC3 and FOXA1. Immunohistochemical staining was performed on primary lesions from 127 patients with ovarian epithelial cancer to detect the expression of HDAC3 and FOXA1. Cell proliferation, migration, and apoptosis were assessed using proliferation assays, Transwell assays, apoptosis assays, and animal experiments before and after FOXA1 transfection. In FIGO stage III-IV ovarian cancer patients, the staining H-scores of FOXA1 and HDAC3 were significantly increased and predicted poor clinical prognosis. The expression level of HDAC3 was significantly correlated with the expression level of FOXA1. In FOXA1 knockdown cells, the invasion, proliferation, and apoptosis capabilities, as well as tumor formation ability, were reduced. Xenograft experiments confirmed that HDAC3 mediates tumor formation. In conclusion, FOXA1 can be regulated by HDAC3 through the Wnt/β-catenin signaling pathway, and FOXA1 plays an important role in the proliferation, apoptosis, and invasion processes in EOC cell lines and xenograft experiments.
To determine the correlation between HDAC3 and FOXA1 expression, researchers performed Western blot experiments. RT-qPCR and Western blot analysis were used to detect the transfection efficiency after transfecting SKOV3 and ES-2 cells with the HDAC3 lentiviral vector (Figure 1A). Western blot results showed that FOXA1 expression levels were significantly decreased in HDAC3 knockdown cells, while they were significantly increased in HDAC3 overexpressing cells. Compared to the corresponding control groups, the expression levels of β-catenin, cyclin D1, and MMP2 were decreased in HDAC3 knockdown cells and significantly increased in HDAC3 overexpressing cells (Figure 1B).
Figure 1. HDAC3 affects FOXA1 and the Wnt/β-catenin signaling pathway. (Lou T, et al., 2022)