Lysine demethylase 3A in hypoxic macrophages promotes ovarian cancer development through regulation of the vascular endothelial growth factor A/Akt signaling

Background: Hypoxia is a vital feature of the tumor microenvironment of OC. Previous evidence exposes that tumor-associated macrophages (TAMs) are connected with the development of ovarian cancer (OC), whereas the accurate regulatory mechanism of hypoxic macrophages regulating tumor advancement remains unclear. Herein, we examined whether the lysine demethylase 3 A (KDM3A) in hypoxic macrophages expedited the development of OC cells.Methods: The contents of hypoxia inducible factor-1 alpha (HIF-1 alpha), CD163, CD80, KDM3A, and p-Akt/Akt were detected by western blot. Genomic Spatial Event 4630, Molecular Signatures Database, and Comparative Toxicogenomics Database were utilized for correlated gene prediction. The OC cells viability was scrutinized by cell counting kit-8 assay. The cell proliferation was inspected by 5-Ethynyl-2 '-deoxyuridine assay. The vascular endothelial growth factor A (VEGF) level was detected by Enzyme-linked immunosorbent assay.Results: M2 polarization of TAMs was associated with poor prognosis in sufferers with OC. The OC sufferers with high level of CD163 or low level of CD80 were linked with poor overall survival and disease specific survival. Hypoxia induced THP-1-derived macrophages M2 polarization. KDM3A was high-expressed in hypoxia induced macrophages. Upregulated KDM3A in hypoxic macrophages facilitated OC cell proliferation. KDM3A upregulation in hypoxic macrophages stimulated Akt signaling activation in OC cells. KDM3A in hypoxic macrophages promoted VEGF secretion to activate Akt signaling in OC cells. VEGF inhibition or Akt signaling inactivation reversed the effects of KDM3A in hypoxic macrophages on OC cells viability and proliferation.Conclusion: The KDM3A content and M2 polarization were enhanced in hypoxic macrophages, and KDM3A in hypoxic macrophages promoted OC development through regulation of the VEGF/Akt signaling pathway.

Automated summary

The lysine demethylase 3 A (KDM3A) in hypoxic macrophages promotes the development of ovarian cancer (OC) cells through the regulation of the VEGF/Akt signaling pathway.