Role of KIF20A Depletion in Inhibiting Ovarian Cancer Progression: Insights From PTEN and M2 Macrophage Polarization

Backgrounds: Recent studies have proven the oncogenic role of kinesin family member 20A ( KIF20A ) in several cancers. Tumor- associated macrophages (TAMs) were reported to participate in tumor initiation and metastasis. In this study, we aimed to explore the detailed mechanism underlying KIF20A in regulating the progression of ovarian cancer and its involvement with TAMs. Methods: KIF20A and phosphatase and tensin homolog ( PTEN ) levels were assessed using reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-2 '-deoxyuridine (EdU) staining assay, colony formation assay, flow cytometry, and western blot were employed to evaluate cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT). The relationship between KIF20A and PTEN was validated using a dual-luciferase assay. M2 macrophage polarization was verified by detecting their markers using RT-qPCR. THP-1 cells were co-cultured with ovarian cancer cells to format TAMs. Results: Ovarian cancer tissues and cells exhibited upregulated KIF20A and downregulated PTEN levels (p < 0.05). Irradiation significantly decreased KIF20A levels (p < 0.05) and blunted the progression of ovarian cancer by reducing cell proliferation and EMT (p < 0.05) and inducing apoptosis (p < 0.05). These effects were augmented by KIF20A depletion (p < 0.05). KIF20A depletion also suppressed ovarian cancer cell progression (p < 0.05). Our findings illustrated that KIF20A negatively regulated PTEN expression in ovarian cancer cells. Moreover, the inhibitory effects of KIF20A depletion on ovarian cancer development in irradiated ovarian cancer cells were obviously impeded by PTEN knockdown (p < 0.05). Additionally, we observed the increased KIF20A expression in M2-like TAMs and its ability to induce M2 macrophage polarization (p < 0.05). Conclusion: KIF20A was found to induce M2 macrophage polarization in ovarian cancer, and KIF20A depletion regulated PTEN to increase radiosensitivity and inhibit ovarian cancer development.