TWIST1 Regulates FOXM1/β-Catenin to Promote the Growth, Migration, and Invasion of Ovarian Cancer Cells by Activating MFAP2

TWIST1 is aberrantly expressed in ovarian cancer (OC). MFAP2 is a downstream target of TWIST1, and we previously found MFAP2 facilitated OC development by activating FOXM1/β-catenin. We planned to investigate the mechanisms of TWIST1 in OC. GEPIA (a database for gene expression analysis) and UALCAN (a database containing comprehensive cancer transcriptome and clinical patient data) investigated TWIST1's connection to MFAP2 and patient survival in ovarian serous cystadenocarcinoma (OV). Human OC cells (A2780 and CAOV3) were transfected with si-TWIST1, oe-TWIST1, oe-MFAP2, or si-TWIST1 + oe-MFAP2. Cellular apoptosis, viability, migration, and invasion were detected. TWIST1, MFAP2, FOXM1, and β-catenin protein expressions were tested. Dual-luciferase and ChIP-qPCR validated the correlation between MFAP2 and TWIST1. Moreover, OC mice were established by injecting OC cells subcutaneously. The pathology, apoptosis, as well as Ki67, TWIST1, MFAP2, FOXM1, and β-catenin protein levels of tumors were assessed. TWIST1 expression positively correlated with MFAP2 expression, but negatively related to patients' survival in OV. TWIST1 overexpression promoted malignant behaviors, and increased MFAP2, FOXM1, and β-catenin protein levels for OC cells. TWIST1 knockdown exhibited the opposite trend. In vivo, TWIST1 knockdown disrupted tissue structure, induced apoptosis, decreased Ki67, TWIST1, MFAP2, FOXM1, and β-catenin protein levels in tumor. Interestingly, MFAP2 overexpression reversed the effects of TWIST1 knockdown in vitro and in vivo. Additionally, dual-luciferase and ChIP-qPCR confirmed MFAP2 was a downstream target for TWIST1 in OC. TWIST1 regulated FOXM1/β-catenin to promote the growth, migration, and invasion of OC cells by activating MFAP2, indicating that targeting TWIST1 may be effective for treating OC.