DNMT1 reduces cisplatin sensitivity partially through downregulating FOXO3a in ovarian cancer cells

Most individuals with ovarian cancer (OC) develop cisplatin resistance while undergoing treatment. Bioinformatic analysis has linked DNA Methyltransferase 1 (DNMT1) to chemoresistance development as well as FOXO3a expression in OC patients. In vitro study results revealed cisplatin treatment could induce DNMT1 expression. Knocking down of DNMT1 could decrease the IC₅₀ of cisplatin. Treatment with cisplatin may reduce FOXO3a expression in OC cells. While in DNMT1 knockdown OC cells, treatment with cisplatin could induce FOXO3a expression. DNMT1 might suppress FOXO3a expression by promoter methylation. FOXO3a overexpression could significantly enhance cisplatin sensitivity. Meta-analysis also revealed opposite effects on OC patients- prognosis: higher expression of DNMT1 is a risk factor for both overall survival and disease-free survival, while high FOXO3a may improve the 5-year survival rate in high-grade serous adenocarcinoma OC patients. Therefore, our results indicated DNMT1 could reduce cisplatin sensitivity in OC cells partially via regulating FOXO3a.