HDAC3 positively regulates HE4 expression to promote ovarian carcinoma progression

Arch Biochem Biophys. 2019 Oct 30:675:108044. doi: 10.1016/j.abb.2019.07.009. Epub 2019 Jul 11.

Abstract

Objective: To identify the relationship between Histone deacetylase 3 (HDAC3) and Human epididymis protein 4 (HE4) and to explore the mechanisms underlying their effects on the malignant behaviors of ovarian carcinoma cells.

Methods: The expression levels of HDAC3 in ovarian carcinoma tissues were identified by immunohistochemistry, Western blot and real-time PCR. A wound healing assay, a Transwell assay and a CCK8 proliferation assay were used to assess the proliferation, invasion and metastatic capacities of ovarian carcinoma cells before and after transfection and HDAC3 protein treatment. HDAC3 and HE4 protein expression level in epithelial ovarian tissues were detected by immunohistochemistry, and the relationship between them was examined.

Results: HE4 was identified as an HDAC3-interacting protein. HDAC3 promotes ovarian carcinoma 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 they were 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 carcinoma and promotes ovarian carcinoma cell proliferation, invasion and migration. HDAC3 and HE4 binding activates the PI3K/AKT signaling pathway, enhances ovarian carcinoma and promotes ovarian carcinoma cell proliferation, invasion and migration. Therefore, inhibiting the relationship between HDAC3 and HE4 may therefore have potential therapeutic value in patients with ovarian carcinoma.

Keywords: HDAC3; HE4; Invasion; Migration; Ovarian carcinoma; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Proliferation
  • Disease Progression
  • Female
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction
  • WAP Four-Disulfide Core Domain Protein 2 / genetics
  • WAP Four-Disulfide Core Domain Protein 2 / metabolism*

Substances

  • RNA, Messenger
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human
  • Proto-Oncogene Proteins c-akt
  • Histone Deacetylases
  • histone deacetylase 3