HDAC3 positively regulates HE4 expression to promote ovarian carcinoma progression

Abstract Objective To identify the relationship between Histone deacetylase 3 (HDAC3) and Human epididymis protein 4 (HE4) and explore the mechanisms underlying their effect on the malignant behaviors of ovarian cancer cells. Methods The expression levels of HDAC3 in ovarian cancer tissues were identified by immunohistochemistry, Western blot and real-time PCR. A wound healing assay, the Transwell assay and CCK8 proliferation assay were used to assess the proliferation, invasion and metastatic abilities of ovarian cancer cells before and after transfection and HDAC3 protein treatment. HDAC3 and HE4 protein expression in epithelial ovarian tissues was detected by immunohistochemistry, and the relation between their expression levels was examined. Results HE4 was identified as an HDAC3-interacting protein. HDAC3 promotes ovarian cancer cell proliferation, invasion and migration by increasing the expression of HE4. HE4 and HDAC3 expression levels were significantly higher in malignant epithelial ovarian tissues than in benign and normal epithelial ovarian tissues. HDAC3 gene interference downregulated the expression of the PI3K/AKT signaling pathway-associated molecules P-PI3K/PI3K and P-AKT/AKT. Conclusion HDAC3 expression is higher in ovarian cancer and promotes ovarian cancer cell proliferation, invasion and migration. HDAC3 and HE4 binding activates the PI3K/AKT signaling pathway, enhances ovarian cancer and promotes ovarian cancer cell proliferation, invasion and migration.