KLHDC8A knockdown in normal ovarian epithelial cells promoted the polarization of pro-tumoral macrophages via the C5a/C5aR/p65 NFκB signaling pathway.

AIMS

Tumor-associated macrophages (TAM) is related to Ovarian cancer (OC) pathogenesis, but the exact mechanism remains unclear. This study investigated the expression of Kelch Domain Containing 8 A (KLHDC8A) in OC and the mechanism associated with TAM.

MAIN METHODS

Bioinformatics analysis of differential expression genes between normal and OC tissues were analyzed based on the Tumor Genome Atlas (TCGA) databases. KLHDC8A mRNA expression was knocked down in normal epithelial cells (IOSE80), and then the effects of siKLHDC8A on the proliferation, invasion, migration and C5a secretion of IOSE80 cells were explored. THP1-derived macrophages were cultured with medium of NC-IOSE80 cells, siKLHDC8A-IOSE80 cells with or without C5aR antagonists.

KEY FINDINGS

KLHDC8A was lowly expressed in OC and negatively correlated with the infiltration of tumor-promoting macrophages, contributing to the survival of OC patients. Furthermore, siKLHDC8A promotes the proliferation, invasion and migration of IOSE80 cells and leads to polarization of pro-tumoral macrophages, which can be rescued by C5aR antagonists.

SIGNIFICANCE

Our results indicated that KLHDC8A knockdown could modulate the development of OC by affecting macrophage polarization to pro-tumoral type via the C5a/C5aR/p65 NFκB signaling pathway. It may play an essential role as the tumor suppressor genes in diagnosis and treatment of OC.